"Kids Conquering Cancer: Flipping the hierarchy to find new diet-based interventions for EGFR and HPV-driven cancers"

Transcript

• 00:00My great pleasure to introduce our
• 00:02grand round speaker doctor Lana Riley.
• 00:04She's the 1st in water.
• 00:06Hope is going to be a long series
• 00:07of lecturers speaking on education,
• 00:09training and career development.
• 00:11This was actually Barbara Burtness idea,
• 00:13so Doctor Riley Hills to us from
• 00:14the Fox Chase Cancer Center where
• 00:16she's in associate professor in
• 00:18the Molecular therapeutics program.
• 00:19She's a scientific director of the
• 00:21immersion science program at Fox Chase,
• 00:23and she's also the executive
• 00:25director of the Eccles Institute,
• 00:28which is a hub where students,
• 00:29teachers and scientists.
• 00:30All joined forces to focus on
• 00:32critical biomedical problems,
• 00:34such as dietary effects on cancer.
• 00:37They're developing,
• 00:37cutting edge projects,
• 00:39and they enhancing scientific leadership
• 00:41within the community in Philadelphia.
• 00:43For for these efforts, Dr.
• 00:45Riley recently received the Elizabeth W.
• 00:47Jones Award for Excellence in Education
• 00:49from the Genetics Society of America.
• 00:51Among her many accolades,
• 00:53she received her pH D in cell and
• 00:55developmental biology at Harvard
• 00:56and a research interest involved
• 00:58nutritional mechanisms that influence
• 01:00stem cell function and development.
• 01:02She's the recipient of multiple NIH
• 01:04awards for her research on stem
• 01:07cells and epithelial homeostasis,
• 01:08and today she's going to be talking
• 01:10to us both about her outreach and
• 01:12education and her own research.
• 01:14In a talk that's entitled kids
• 01:16conquering cancer,
• 01:17flipping the hierarchy to find
• 01:19new diet based interventions for
• 01:21EGFR and HPV driven cancers.
• 01:23So, without further ado,
• 01:24it's my pleasure to turn the
• 01:26platform over to Doctor O'Reilly.
• 01:33It's really a pleasure to be here
• 01:34and thank you for inviting me.
• 01:36I'm also my very first research mentor.
• 01:40Anton Bennett is one of your faculty
• 01:43members and everything I know I
• 01:45learned from Anton and Venelles lab.
• 01:47So yeah, today I'm going to talk to
• 01:50you about mostly about our diet based
• 01:52programs involving high school students.
• 01:55So one of the things I want you all to start
• 01:58thinking about as we start here is why.
• 02:00Why did you enter science?
• 02:02A lot of times you know people ask
• 02:04us this question in all kinds of
• 02:07different applications and most of
• 02:09the answers are fairly similar.
• 02:11A little bit canned.
• 02:12I've loved science since childhood.
• 02:14I like to answer questions.
• 02:17I have some aspect of love love,
• 02:20love for science here or I care
• 02:23about somebody very much.
• 02:24So one of the things that we wanna
• 02:26do is to connect these puzzle pieces
• 02:28together to make an inclusive environment
• 02:30so that everyone can participate.
• 02:32So why do we even want inclusion?
• 02:34Why does it matter if we're all kind of
• 02:36similar people with similar ideas and
• 02:38we're going to work together better, right?
• 02:40But but that sort of limits our discoveries,
• 02:43right?
• 02:43So if we don't embrace.
• 02:45The life experiences and knowledge
• 02:47of all different types of people.
• 02:49Then we're essentially missing things
• 02:51that we could otherwise gather together.
• 02:54So why is inclusion so hard?
• 02:56Why is it so hard like we keep hearing
• 02:59about diversity, equity inclusion efforts,
• 03:02and failing and failing and failing?
• 03:05Why? Why is this so hard?
• 03:07So one of the really big problems we have,
• 03:10especially in a city like Philadelphia,
• 03:11which is 80% underrepresented
• 03:14minorities in science,
• 03:16is that we have a major attrition
• 03:19of scientists as they move up in
• 03:22the in the scientific pipeline.
• 03:24So in terms of bachelors degrees,
• 03:26it's still under representation,
• 03:27but this number plummets by
• 03:29the time you get to postdocs.
• 03:32And then there has been exactly
• 03:330 gains in full professors for
• 03:36underrepresented minorities.
• 03:38In many decades. So what's the deal?
• 03:41Why is this happening?
• 03:42One of the reasons is this why the
• 03:45the why that people who are minority
• 03:47scientists enter this field is to
• 03:50help address health challenges
• 03:52of their own communities,
• 03:55and so the topic choice in papers recently
• 03:57published by the NIH about their own grants,
• 04:00shows that awards to African American
• 04:02and black scientists are prohibitively
• 04:04low because of the topic choice of
• 04:06addressing the health disparities
• 04:08that plague their own communities.
• 04:10And this.
• 04:11Makes no sense,
• 04:12right?
• 04:13This makes no sense,
• 04:14but recruiting people into science to
• 04:17address the problems that other people
• 04:19can address and then pushing them out
• 04:21by not allowing them to have funding.
• 04:23So these are both very excellent papers
• 04:25for anyone who is interested in this
• 04:28topic and wants to read more about it.
• 04:30So this lack of representation in
• 04:32science and medicine is a primary
• 04:34driver of health disparities.
• 04:35Just recently,
• 04:36if we highlight the COVID-19
• 04:39pandemic the underrepresentation
• 04:41in science is exactly reflected by the
• 04:43numbers of deaths of COVID-19 with black
• 04:46Americans having the highest rates of
• 04:49death and the lowest representation.
• 04:51This is the same across all chronic diseases,
• 04:54including cardiovascular disease,
• 04:56hypertension, diabetes, and and also cancer.
• 05:01So here in Philadelphia,
• 05:03our demographics are flipped from the
• 05:05predominant demographics in science,
• 05:07where 70% of US faculty research
• 05:11scientists are white. In contrast,
• 05:14only 5% or fewer are African American or
• 05:17black in the school district of Philadelphia.
• 05:20This is opposite, so our predominant
• 05:23populations are black and Hispanic,
• 05:25and these students essentially have no
• 05:27chance of achieving a research career
• 05:30given the predominant prevailing culture.
• 05:33So this is something that we want to change.
• 05:35This first of all,
• 05:36is not fair and second of all,
• 05:38puts people in a situation if they
• 05:40don't even try to pursue science
• 05:42because they know they have no chance.
• 05:44And our goal is to try to help Philadelphia
• 05:46address these health disparities in COVID-19,
• 05:48cancer, diabetes,
• 05:50and Alzheimer's that are are really
• 05:54destroying their communities.
• 05:56So how are we going to do this?
• 05:58We already know that 77% of college students
• 06:02switch out of STEM majors after one semester,
• 06:04we created a program where 72% of
• 06:07our graduates actually continue
• 06:09conducting paid research in college
• 06:11completely flipping these numbers.
• 06:14Fewer than 6% of Philadelphia and other
• 06:17inner city students complete their
• 06:19stem degrees with fewer than 10% of
• 06:21those completing graduate degrees.
• 06:23In contrast, 100% of our students
• 06:26complete their stem degrees on time.
• 06:28So how do we do this?
• 06:29This is a big change, right?
• 06:31A big change.
• 06:32So we created a program
• 06:35built on citizen science.
• 06:37So a staircase of discovery
• 06:39is comprised of four steps.
• 06:41Which level one is crowdsourcing,
• 06:43and many people have heard of apps where
• 06:45people can measure clouds, and you know,
• 06:47say how many animals they saw.
• 06:50In the woods near their house.
• 06:51So it's sort of like like an observation
• 06:54where the data gets transmitted back
• 06:56to scientists who interpret it.
• 06:58The second level is distributed intelligence,
• 07:00so this the citizens can actually
• 07:02collect the data and start to
• 07:04think about what it means.
• 07:05Then participatory science,
• 07:07where the students or participants
• 07:11define the problems that participate
• 07:13in the data collection,
• 07:14and then finally where they're basically
• 07:17independent scientists like like all of us.
• 07:19So we created a program that
• 07:22matches these steps,
• 07:23starting with students as
• 07:24young as fifth grade.
• 07:26So our primary participants
• 07:27are 5th to 12th grade.
• 07:29They start in school,
• 07:31they do their first research
• 07:32experience in school,
• 07:33then they can continue focusing on a
• 07:37junk food diet more in their classroom,
• 07:40summer camps and undergraduate bridge to
• 07:42research that's built on a graduate rotation,
• 07:44and finally independent
• 07:46research and foxchase labs.
• 07:48And by the time they're ready
• 07:49to go to college.
• 07:50Remember,
• 07:50this is just before college.
• 07:52They already have up to two years of
• 07:55research experience under their belt
• 07:57and tend to get paid research positions
• 07:59their first year of college,
• 08:00and then they go up from there.
• 08:04So we started this program in 2013.
• 08:06This is Darius well and she's the science
• 08:09educator, curriculum guru genius,
• 08:11who created basically translates how we
• 08:14do Advanced Research into something that
• 08:16can be done in high school classrooms.
• 08:20And since 2013 we've trained over
• 08:222000 students using this method.
• 08:25This is 570 of them on the steps
• 08:27of the Franklin Institute,
• 08:28where they came to present their
• 08:30Cancer Research data in 2019.
• 08:33As a collective group sharing with each
• 08:36other with scientists with the community
• 08:38that there are 18 new cancer gene
• 08:41hits of nutrients that affect cancer.
• 08:43We're also collecting tons of education,
• 08:45data points, and 60% of these new
• 08:49scientists are underrepresented.
• 08:51Currently in biomedical research.
• 08:54So does it actually work?
• 08:56Do the students want to continue so this
• 08:58is a kind of a complicated diagram,
• 09:00but just focus on the the Blues and the Reds,
• 09:03which are the bad things, right?
• 09:04You don't see much blue and red
• 09:06in any of these pie charts,
• 09:07indicating that the students make
• 09:09tremendous gains in life skills,
• 09:11including peer collaboration,
• 09:12confidence adjusting to projects,
• 09:14and thinking outside the box that
• 09:16they can apply to any career.
• 09:17And keep in mind that these students
• 09:19are unselected.
• 09:20This is a bunch of 9th, 10th,
• 09:2111th and 12th graders who are taking a class.
• 09:24Their teacher decided to participate
• 09:26in the program.
• 09:27They are not pre selected or filled out.
• 09:29An application saying they're
• 09:30interested in science,
• 09:31so this is actually a fairly.
• 09:35A fairly huge gain.
• 09:37He also made gains in research skills,
• 09:40how studying the topic
• 09:41addresses real-world issues,
• 09:42which is something that's
• 09:44incredibly important given the
• 09:45COVID-19 pandemic and other issues.
• 09:48How to formulate a hypothesis,
• 09:49explain projects and and prepare
• 09:51and present their work and then
• 09:54finally the the most important part
• 09:56perhaps is inclusion and interest,
• 09:59whereas students think and feel
• 10:01like a scientist.
• 10:02We have a little work to do on
• 10:04feeling like part of the scientific
• 10:07community to make sure that that
• 10:09that number that red bar goes down
• 10:11and then this was something that we
• 10:13never in a million years expected.
• 10:14We sort of expected.
• 10:16Maybe 20% would be interested
• 10:17in being a scientist.
• 10:18But 56% saying maybe was mind blowing, right?
• 10:22Think about all of the things
• 10:24these kids could be and now just
• 10:25from this one little experience,
• 10:26they're thinking.
• 10:27Maybe I want to be a scientist and even more,
• 10:30the numbers are even higher for
• 10:31students who want to do more research,
• 10:33emphasizing the disconnect between
• 10:35what students think of as science
• 10:38and now what they know as research.
• 10:41So in 2019 we had over 1000
• 10:44students in one run,
• 10:45our biggest auditorium at Fox
• 10:47Chase only holds 320 people.
• 10:49So we created a nonprofit organization
• 10:52called the E close Institute,
• 10:54which is a hub where students,
• 10:57teachers, scientists,
• 10:58community,
• 10:58and hopefully we'll be building
• 11:01accessible databases for everyone,
• 11:03come together to try to solve
• 11:06these community health problems.
• 11:08So we have summer camps where
• 11:11students participate for a
• 11:13week, really delving into
• 11:14high level techniques,
• 11:16including running gels, doing microscopy,
• 11:19lots of pipetting and measuring skills.
• 11:23And in in the summer camps again,
• 11:25more even more students want to be
• 11:28scientists with nobody saying they no.
• 11:30Nobody said no,
• 11:31I don't ever want to be a scientist.
• 11:33And 90% of the students
• 11:35want to do more research.
• 11:36And so one of the things I think we
• 11:38need to think about in general is how to
• 11:41infuse research into more other subjects.
• 11:43Because the students love doing the research,
• 11:45even those who don't necessarily
• 11:47want to be scientists.
• 11:49So this is our undergraduate
• 11:50bridge to research.
• 11:51This is actually where we started
• 11:52in 2013 and we have 230 students
• 11:55who've now completed this program.
• 11:58They have started to grow up
• 12:00now since we started in 2013.
• 12:02We have 16% in medical school
• 12:05and absolutely shocking 17.3%
• 12:08pursuing PHD's in biomedicine.
• 12:11We have a number of them who are doing
• 12:14gap years in research labs 22 percent,
• 12:1718% are engineers and 6%.
• 12:19Are in other stem related careers,
• 12:21especially business entrepreneurship,
• 12:24math type stuff?
• 12:27So yeah,
• 12:27so since this has been working so well,
• 12:29we expanded this to be true
• 12:31community science.
• 12:31Having an out outreach citizen science
• 12:34event in the fall where we had church
• 12:38members and kids and families.
• 12:40Oh that's all blurry,
• 12:42all participating in providing
• 12:44their thoughts,
• 12:45their ideas and their input and how
• 12:48to solve the problem of diabetes.
• 12:51And in the Philadelphia community.
• 12:55So how does this all work? Like?
• 12:56Why is this working better than other
• 12:58things and the the key thing is the Y.
• 13:01So this is a. This is a a video of
• 13:04one of our presenters that emphasizes
• 13:08the importance of the why this
• 13:10project I was most interested in
• 13:12studying squamous cell carcinoma,
• 13:14which is a type of skin cancer that affects
• 13:16over a million people in the US every year.
• 13:18One of those people was my grandmother
• 13:19who I lost to disease in 2015.
• 13:21You might notice a small blue butterfly
• 13:23floating around front presentation,
• 13:24that's why. Joining us today.
• 13:28So one of the most important things
• 13:31for our students is that they are
• 13:33here to cure somebody they love,
• 13:35and so one of the things I think
• 13:37we lose sight of as scientists
• 13:39in our training is is that why?
• 13:41So we come in? Oh yeah,
• 13:43that's great that you came in
• 13:45because your your zeami is sick.
• 13:47But here's how we do things here.
• 13:48Here's the project I'm giving you
• 13:50and so this is something I want
• 13:52everybody here to really start
• 13:54thinking about is do you know what
• 13:56the why is for all of your trainees?
• 13:58Does it matter right?
• 14:00Is that why they're still here?
• 14:01Is that what's driving them to
• 14:03succeed in a very difficult,
• 14:05particularly funding environment?
• 14:06And is that something that that can be
• 14:10leveraged to identify new ways to treat,
• 14:13you know,
• 14:14treat and prevent cancer or other diseases?
• 14:17So diet is a particularly accessible.
• 14:20Topic for children.
• 14:21Everybody knows what's good to eat,
• 14:24what's bad to eat.
• 14:26Children in particular have body image
• 14:28challenges and then many people in
• 14:30their families also have more advanced
• 14:32diseases like diabetes and cancer
• 14:34that they want to understand and help.
• 14:36So we start with the question
• 14:39of what should I eat?
• 14:40Our main goal is to improve research literacy
• 14:42so that students understand what research is,
• 14:45how it's conducted,
• 14:46what the vocabulary is,
• 14:48what's expected of them and including that.
• 14:51The existing hierarchy.
• 14:53So the the program is student centered,
• 14:55it's transdisciplinary.
• 14:56It promotes self efficacy of each
• 14:59and every student and it improves
• 15:01the agency of the instructors and
• 15:04the students to take charge of their
• 15:06own research questions and projects.
• 15:11So why diet? Why does diet matter?
• 15:14You know my my research lab
• 15:16works on how nutrients impact
• 15:18signal transduction pathways,
• 15:19which is the core of how we
• 15:22started and in this area.
• 15:24For this large scale outreach program and
• 15:27diet is unambiguously a key to health,
• 15:30so this is a current sort of
• 15:32diagram of the recommendations for
• 15:33a healthy diet where you have.
• 15:36Lots of fruits and vegetables.
• 15:38Probably too many grains.
• 15:39A small amount of of meat and
• 15:42protein products and some dairy
• 15:43with a very tiny little pie.
• 15:46Slice of junk food here.
• 15:48And I think most people
• 15:50don't really eat this.
• 15:52Most people.
• 15:52It's a little bit expanded down
• 15:54here on this end and reduced
• 15:56a lot here on this end,
• 15:57but this type of healthy diet
• 15:59is known to reduce the symptoms
• 16:01of aging and to promote healthy
• 16:03aging throughout the lifetime.
• 16:05So we all know, right?
• 16:07We all know what we should be eating,
• 16:08but we don't always do that.
• 16:10So what do we do? How do?
• 16:11How do we make this better?
• 16:13There's diets.
• 16:14Dietary cookbooks that are about longevity,
• 16:18reducing calories, eat less,
• 16:20live longer, and this.
• 16:22These diets are actually very,
• 16:24very well supported by basic
• 16:25science data showing that in every
• 16:28Organism caloric restriction extends
• 16:30lifespan and improves health.
• 16:33Most recently, intermittent feeding.
• 16:35Is is another,
• 16:38probably much easier way to reduce
• 16:41the the metabolism challenges that
• 16:43occur during unhealthy aging in a
• 16:46similar way to caloric restriction and so,
• 16:49so how do we leverage these types of diets?
• 16:52Is intermittent feeding a good thing for
• 16:54for a young teenager with a body image issue?
• 16:57Probably not.
• 16:57So how do we start to have the conversations?
• 17:00How do we promote health through
• 17:02diet and how do we leverage chemicals
• 17:04in the diet to try to improve?
• 17:07Existing therapies so another really cool
• 17:09thing about diet is it's very cultural,
• 17:11so every religion has very
• 17:15specific dietary recommendations.
• 17:17There is herbal medicine that is widely
• 17:19used in almost all areas of the world
• 17:22and then just think about where you're from,
• 17:24right?
• 17:25So there's some kind of a cultural
• 17:27cuisine where you're from.
• 17:28That is something that's to
• 17:30be celebrated in holidays.
• 17:31And all of these things,
• 17:32so why not celebrate those
• 17:34same things to promote health?
• 17:38So in the United States,
• 17:39a lot of people do.
• 17:40The herbal medicine type thing
• 17:43using dietary supplements,
• 17:44and just as a as as a thing to note,
• 17:47dietary supplements are
• 17:49not regulated by the FDA.
• 17:51The FDA is not authorized to
• 17:53review dietary supplement
• 17:54products before they are marketed,
• 17:56and so we are relying completely
• 17:58on manufacturers and distributors
• 17:59to make sure the products are
• 18:01safe before they go to market.
• 18:03So no, dietary supplements are
• 18:05regulated by the government.
• 18:0770% of cancer patients are
• 18:08using dietary supplements.
• 18:10Compared to 56.6% of the general population,
• 18:13this is an extraordinarily high number.
• 18:16These studies were done on
• 18:18predominantly white patients with
• 18:20very few I couldn't actually
• 18:22find any studies that were done
• 18:24exclusively on minority patients.
• 18:26The one study I did find said
• 18:29that 76.3% of Hispanic patients
• 18:30do not tell their doctor that
• 18:32they're taking the supplements,
• 18:34which I think is true for most people.
• 18:37So this is something that's
• 18:39also important to.
• 18:40Consider is that people are
• 18:42taking stuff that might be
• 18:44interrupting the the therapy
• 18:46that they're being prescribed.
• 18:48So what's our goal?
• 18:49Our goal is to understand how every
• 18:51chemical that you can consume as part
• 18:53of a diet impacts signal transduction
• 18:55pathways that are involved in disease.
• 18:58So this is a proteome diagram from Joseph LA.
• 19:02So the entire Drosophila genome.
• 19:06Translated into proteins
• 19:07with interaction maps here.
• 19:09So what we would like to do is
• 19:11take each and every compound that's
• 19:13found in the diet and identify those
• 19:15that inhibit or activate individual
• 19:17proteins to create a new diet map
• 19:20on top of the proteome map so that
• 19:23we can create tailored diets for
• 19:25individual diseases based on the genetics,
• 19:28the protein expression,
• 19:30and the the dietary access of the patient.
• 19:34So that's obviously an
• 19:36extremely daunting task,
• 19:37like it's something where our usual
• 19:39one protein one project 1 mechanism,
• 19:42one person is not going to work,
• 19:44and so this is one of the reasons
• 19:47that we think that.
• 19:48Getting high school students involved,
• 19:51which is a population that's
• 19:53eager and in desperate need of
• 19:55having these types of experiences.
• 19:57We have 16 million high school
• 19:58students in the United States
• 20:00with fifty 550 million worldwide.
• 20:02So suddenly a daunting task maybe
• 20:04becomes a little bit more feasible.
• 20:06Each of these students comes from
• 20:08a family that eats right.
• 20:10They have their own particular types
• 20:12of cuisine that are important to them,
• 20:14some of which may have chemical
• 20:17compounds that can inhibit.
• 20:18Cancer signaling pathways to enhance
• 20:21the efficacy of existing therapies.
• 20:25So how do we do this?
• 20:27We have a bunch of dietary supplements or
• 20:29other things that the students bring in.
• 20:32We feed them to fruit flies,
• 20:34either wild type fruit flies or flys
• 20:36bearing mutations in oncogenes,
• 20:38tumor suppressor genes,
• 20:39or more recently in pathways
• 20:41related to diabetes.
• 20:43And then we screen to see what happens to
• 20:45the developmental life cycle of the fly.
• 20:47So do they continue to lay eggs?
• 20:49Do they develop into pupae and
• 20:52then do they close as adults?
• 20:55And So what we found is the most
• 20:57reproducible assay is counting the the
• 20:59number of pupae on the side of the vial.
• 21:02So you can see here.
• 21:03These are like the little larvae,
• 21:04and then they crawl up and become pupa
• 21:07like a chrysalis for a butterfly.
• 21:10And if we have hundreds of people
• 21:13scoring the same exact sample,
• 21:15we actually get pretty tight.
• 21:17Pretty tight statistics for
• 21:19determining the the numbers of pupae,
• 21:22and so you can clearly see that
• 21:24wild type can be compared to loss
• 21:26of function mutants in P-10,
• 21:27which are fairly similar to gain of
• 21:30function mutants in PI3 kinase which
• 21:32are in the same related pathway.
• 21:34Things like the FOXO mutants have
• 21:36much more broad variability,
• 21:38so it's going to be a little
• 21:40bit more difficult to interpret.
• 21:41The results of those experiments,
• 21:43so this type of experiment could
• 21:44be done with any gene that anybody
• 21:46is interested in,
• 21:47for which there is a mutant in the fly model.
• 21:52So we focus with the students initially
• 21:55on basics, so signal transduction.
• 21:56You have a leg and you have a receptor.
• 21:59You have an effect.
• 22:00Are you drive proliferation
• 22:01that causes cancer?
• 22:02Keep it simple and a cancer passed away.
• 22:04You could have too much lag and
• 22:06that drives the whole pathway.
• 22:07You can mutate the receptor or
• 22:08you can have a mutant effector,
• 22:10all of which will give the same outcome
• 22:13of having too much proliferation.
• 22:16So it since 2013 we've had a big
• 22:19project on the EGF receptor pathway and
• 22:21all of the genes that you see here.
• 22:24We have representative viable mutations
• 22:26and flies which are modifiable.
• 22:29Meaning if a compound makes the
• 22:33phenotype worse, that will be detected.
• 22:35If the compound makes the phenotype better,
• 22:37that will be detected because these are
• 22:39mutants that are not complete nulls,
• 22:41so the the great thing about this is
• 22:43that many high schools have eight
• 22:45groups of students who are doing experiments.
• 22:48Together so we give them sequential
• 22:50mutants in the EGF receptor signaling
• 22:52pathway.
• 22:53Have them screen the same drugs
• 22:55and in doing so we can map exactly
• 22:58which of the components of the
• 23:01signaling pathway are affected.
• 23:05So in order to approve the
• 23:07proof of principle for this,
• 23:08we started by treating flies with gefitinib,
• 23:11which is an inhibitor of the EGF receptor,
• 23:14and what happens is the same thing that
• 23:16happens if you have a loss of function,
• 23:18EGF receptor mutant, which is you
• 23:20fuse these respiratory structures
• 23:22called dorsal appendages on the egg,
• 23:25so in a wild type there are two
• 23:26and in a in a gefitinib treated
• 23:28or an EGF receptor mutant.
• 23:30There's only one.
• 23:32So this is a very robust,
• 23:33easy to score phenotype for anybody,
• 23:35just even using a magnifying glass.
• 23:37And then we screened a bunch of
• 23:40different kinase inhibitors and
• 23:41the ones in red are known, e.g.,
• 23:43F receptor inhibitors and you can see
• 23:45that all of them had some effect on
• 23:48induction of dorsal appendage fusion.
• 23:50There were a couple others imatinib
• 23:52which inhibits ABL kinase and miss
• 23:55it nib which inhibits VEGF receptor.
• 23:58Also had had effects which is something
• 24:00will follow up at some time later.
• 24:02Uhm, we also noticed that at a
• 24:06low dose of gefitinib you have
• 24:07the dorsal appendage defects,
• 24:09but normal numbers of eggs.
• 24:10If you increase the dose now,
• 24:12you reduce the numbers of eggs,
• 24:13which turns out to be a much more
• 24:15easy and robust to score phenotype,
• 24:17which is loss of development.
• 24:20And then finally,
• 24:22there's excellent reagents for
• 24:24measuring downstream signaling,
• 24:25including Erk activity,
• 24:26so here is no good fit in.
• 24:28If you see nice Erk activity and
• 24:30as soon as you start adding the
• 24:32gefitinib you you inhibit the Erk
• 24:34downstream of the EGF receptor
• 24:36and you know these are like the
• 24:38students learn how to do this and
• 24:39they do it once and so you get some
• 24:42variability in the loading but.
• 24:44At the end of the day,
• 24:45what we're looking for is something to
• 24:47pursue in a professional lab down the road.
• 24:50So once the students started
• 24:52screening the dietary supplements,
• 24:53the first thing that popped
• 24:55out with Selena methionine,
• 24:56which gives an EGF receptor like
• 24:58phenotype of a single dorsal appendage.
• 25:00You also see dramatically reduced
• 25:03numbers of pupil pupil cases,
• 25:05meaning that the Salina methionine
• 25:07is behaving like a high dose of
• 25:09gefitinib innocence of reducing
• 25:11the numbers of eggs laid.
• 25:15So in order to figure out if this was real,
• 25:17so one student doesn't mean it's right,
• 25:20they could have killed everything, right?
• 25:21Like you, you just don't know.
• 25:23So we put this into a classroom project.
• 25:26For this 570 students I showed
• 25:27you on the steps of the Franklin
• 25:30Institute and they screened.
• 25:32All of the steps in the EGF
• 25:35receptor signaling pathway.
• 25:37Mutants in all of these different
• 25:39steps for effects by selenium and
• 25:41what we see is that the high dose of
• 25:45selenomethionine basically affects everybody,
• 25:47meaning it's probably toxic for any fly,
• 25:50but the low dose was actually quite
• 25:52variable such that only rats and Corkscrew,
• 25:55which is the fly homologue of
• 25:57the tyrosine phosphatase SHP two,
• 25:58were the only two affected and they
• 26:00were affected in opposite ways.
• 26:02Such that the wrasse mutants were
• 26:04less viable and the Corkscrew mutants
• 26:07were more viable upon treatment
• 26:09with Selena methionine.
• 26:11So then we use the Erk activation again.
• 26:14Here's wild type.
• 26:15This is the activated EGF receptor
• 26:17mutant you see a dramatic increase.
• 26:19We can also do this by immunostaining
• 26:22to see specifically which cells
• 26:25are affected by various treatments
• 26:27and what we found here is that
• 26:30the which was a surprise.
• 26:32We expected the Salina methionine
• 26:34to reduce the arc activity instead.
• 26:36If you compare the wild type here
• 26:38in lane one to this lane over here,
• 26:41this Lena methionine.
• 26:43Actually blasted the Erk signaling bypassing
• 26:47any type of inhibition of VEGF receptor so.
• 26:52This turned out to be true in
• 26:54multiple different cancer cells,
• 26:55which the students went on to do
• 26:57in foxchase labs in the summer.
• 26:59So breast cancer,
• 27:00colorectal cancer,
• 27:01and pancreatic cancer with
• 27:02gain of function RASP mutations
• 27:04all showed the similar effect,
• 27:06with SELENOMETHIONINE actually increasing
• 27:08Erk activity up until at least in
• 27:12two cases the dose got too high.
• 27:14On K CO2 which is a non rast dependent
• 27:17colorectal cancer cell line had less
• 27:19of an effect suggesting that like in
• 27:22the fly the gain of function wrasse
• 27:25mutations make the the cells more
• 27:28sensitive to this Selena methionine effect.
• 27:31So we've done this with it.
• 27:32We're still in the process of
• 27:34finishing finishing this project.
• 27:36Over 300 students have worked on it,
• 27:39in addition to the 1001 students who
• 27:41did the screening in the classrooms.
• 27:43So it's going to be a lot of authors
• 27:46on the paper that we're planning
• 27:47to publish this year,
• 27:48but we have a number of other
• 27:50compounds that inhibit specific
• 27:51components of this pathway,
• 27:52so burdock root is a very potent
• 27:55inhibitor in this case of AKT.
• 27:59Butcher's Broom is an activator of Corkscrew,
• 28:02as is Selena methionine and grape seed
• 28:06extract inhibits raft, so so this is
• 28:09something where you can see like.
• 28:10Eventually we will kind of have a a really
• 28:13nice map of this particular pathway and the
• 28:15different compounds that that can affect it.
• 28:18So this was a project that I
• 28:20designed thinking it's accessible.
• 28:22It's easy, it's straightforward.
• 28:23It's part of the curriculum for the students.
• 28:26What they need to learn in high school,
• 28:28and then we started having students
• 28:30come in with their own ideas.
• 28:31So one student brought in apricot seeds,
• 28:33which is mom who was a breast cancer
• 28:36survivor was taking as God's cure for cancer.
• 28:39It turns out as soon as you digest this,
• 28:41it turns into a molecule of cyanide
• 28:43and a molecule of benzaldehyde and
• 28:45women who are taking this are dying
• 28:48of cyanide poisoning.
• 28:49So this is a really serious public
• 28:51health issue that nobody reports to
• 28:52their doctor 'cause as soon as you tell
• 28:55your doctor I'm taking apricot seeds,
• 28:56they say you can die from cyanide poisoning.
• 29:00So, so this is something that's
• 29:02essentially people taking poison
• 29:04that needs to be addressed.
• 29:06Another student came in.
• 29:07Saying that her grandfather had stage
• 29:09four lung cancer and was eating 100
• 29:11live weevils in a glass of Sprite
• 29:14every day and it cured his stage.
• 29:16Four lung cancer and so this is,
• 29:19you know,
• 29:19another curiosity like you.
• 29:20Don't just tell people you shouldn't
• 29:22do that like we need to figure this
• 29:24out and it turns out what she found
• 29:26out was that the defense chemicals
• 29:27secreted by these weevils when
• 29:29they get dropped into a glass of
• 29:30Sprite are actually very potent.
• 29:32Chemotherapeutics against lung cancer.
• 29:34So so this is something where
• 29:36there's truth and there's danger.
• 29:38In in the same thing and these are not
• 29:40things that most scientists would be like.
• 29:42Oh let's go investigate weevils so so
• 29:45these are things that are happening
• 29:47in our communities that we don't know
• 29:49about and are extremely important.
• 29:51And finally,
• 29:51just last summer we had a kid come
• 29:53in who was interested in lean,
• 29:55which is a combination of codeine
• 29:58based cough syrup and Sprite.
• 30:00And kids are using this to get high
• 30:02and he was very concerned that his
• 30:04friends who were all doing this because
• 30:07it's healthier than taking drugs.
• 30:09We're going to get brain cancer and
• 30:11so these are the sorts of things that
• 30:13are going on that the students want
• 30:14to research because it's affecting
• 30:16the people they love and we don't
• 30:18want to bring them in and tell them
• 30:21that's not important because.
• 30:22This is important.
• 30:25So this is a project at all.
• 30:28I'll just highlight a lot,
• 30:29which is a a project designed by 5
• 30:32young ladies starting with Eliana here
• 30:34who was doing a cultural awareness
• 30:36project to find out what cancers
• 30:39particularly affect people from Puerto Rico,
• 30:41and So what she found is that Puerto
• 30:44Ricans have an extremely high rate
• 30:46of HPV based cervical
• 30:47cancer. Even though Hispanic
• 30:49girls were more like likely to
• 30:50get vaccinated than white girls,
• 30:52and so this was something that
• 30:54was really bothering her,
• 30:55so most of the studies have been
• 30:57done on HPV types 16 and 18.
• 30:59So here's 8100 cases of this.
• 31:03But it turns out that in
• 31:04Hispanic and black communities,
• 31:06other strains of HPV are more prevalent,
• 31:08and so these are not small numbers.
• 31:11So 1800 from these types,
• 31:14and then another 1200 from these
• 31:16types is is not a small number,
• 31:18and it turns out that many of these
• 31:20strains of the virus are not actually
• 31:22protected by available vaccines,
• 31:24so so this started a conversation
• 31:27among these predominantly minority
• 31:29women of what's going on with this.
• 31:31So there's a lot of.
• 31:34You know,
• 31:35sort of social reasons for for pointing
• 31:37fingers at why health disparities exist.
• 31:40So a lot of it has to do with poverty,
• 31:44access to health care and various
• 31:46life choices that are generally
• 31:49considered explanations for why
• 31:50these health disparities exist.
• 31:52But Eliana's discovery,
• 31:53sort of made it seem like maybe
• 31:56there's some genetic basis
• 31:57to some of these differences.
• 31:59So Nicole Harrington came in
• 32:01with this concept that black
• 32:03mothers don't trust the medical
• 32:05community enough to get vaccinated,
• 32:07and so this is an example for the
• 32:09COVID-19 vaccine where you can
• 32:11see that black Americans had a
• 32:13very very low vaccination rate
• 32:15compared to white Americans.
• 32:17And similarly for the HPV vaccine,
• 32:20the same thing is true where?
• 32:23Hispanic and and black Americans are
• 32:26less likely to get vaccinated and
• 32:28then what we also need to really
• 32:32realize is that they they think the
• 32:35vaccine is harmful and even more that.
• 32:39You know?
• 32:39They think people are being treated
• 32:41like Guinea pigs by scientists like us,
• 32:44so so this is a really big issue
• 32:46in terms of how to get information
• 32:48out how to reduce this mistrust
• 32:50and our take on this is that we
• 32:52need to increase representation and
• 32:55understanding of the fears that the
• 32:58public has about these vaccines.
• 33:02So then we went down to the
• 33:04cellular molecular level,
• 33:05so HPV happens with a.
• 33:08Initial infection,
• 33:09but the virus can move into sort
• 33:13of the the basic sort of stem
• 33:17cell areas of the of the cervix,
• 33:19and then it can just hang out for
• 33:22awhile and then eventually it
• 33:24can come out and create invasive
• 33:27neoplasia and so this is a pathway
• 33:29that's that's basically mediated
• 33:31by inhibition of P53 and RB,
• 33:33which are two proteins that
• 33:35control the cell cycle,
• 33:37and so two students neelys and Allison.
• 33:40Decided to screen dietary supplements
• 33:42to find something that would kill
• 33:44flies bearing mutations in P53 or
• 33:46RB to sort of mimic virus infection
• 33:48and what they found was multiple
• 33:51components that drive a process
• 33:53called ferroptosis which is a
• 33:55type of iron dependent cell death
• 33:57and you can see here that.
• 33:59The P53 null flies are highly
• 34:02susceptible to acetaminophen,
• 34:04which is Tylenol or iron in
• 34:06terms of being killed.
• 34:08And then they went on and did a dose curve
• 34:10to find doses that really had little or
• 34:13no effect on wild type but still were
• 34:15were potent for RB and P53 mutants.
• 34:18And so we're very interested in this kind of
• 34:21idea that they came up with from their own.
• 34:24Experiences, and it turns out that
• 34:27HPV inhibits a receptor that is a
• 34:30major controller of of ferroptosis
• 34:33through a protein called G.
• 34:36PX4P53 is also a regulator of this process.
• 34:38Acetaminophen, which is one of the
• 34:41things that scored in the screen
• 34:43actually affects this whole process,
• 34:45and so a colleague of mine,
• 34:47Jeff Peterson, who's also at Fox Chase,
• 34:49is a lab that studies ferroptosis,
• 34:51and so they had two compounds, ESA.
• 34:54And harassed in that act in different
• 34:56ways to induce ferroptosis.
• 34:59And so we wanted to see.
• 35:01Whether the observations that the
• 35:03students made in the fly would be true
• 35:06also in HPV depending cancer cells,
• 35:08so this was done by Jesse Rynok with
• 35:11the help of postdoc and Jeff Slabtown
• 35:13who sing and what we see is differential
• 35:17sensitivity to the ESA compound,
• 35:20such that in cervical cancer cells,
• 35:23HPV positive cells are resistant to
• 35:25induction of ferroptosis and in the
• 35:27head and neck cancer cells there
• 35:29are actually more sensitive.
• 35:31And so this is something that we're
• 35:33trying to figure out now, like,
• 35:35what is the difference between these?
• 35:36And obviously the cells have more
• 35:38things going on in them other than
• 35:41just HPV infection.
• 35:42But we know that this was actually
• 35:45ferroptosis process because if you
• 35:47add an inhibitor of ferroptosis
• 35:49then you abrogated the the response.
• 35:53So using a different inducer of Ferroptosis,
• 35:57Calder,
• 35:57Aston there didn't seem to be any
• 36:00effect at all on HPV minus head
• 36:02and neck cancer cells,
• 36:04but there really was a dose dependent
• 36:08reduction increase in killing basically
• 36:10of the HPV positive cells that Jesse is
• 36:13going to be further exploring this summer.
• 36:16So the two projects together maybe actually
• 36:20centered on on one particular thing,
• 36:22which is selenium.
• 36:23Uh, which is an activator of GPX 4G.
• 36:27P X4 is a selenium dependent protein that
• 36:29prevents the production of lipid radicals,
• 36:32which are what causes this ferroptosis
• 36:35and at the same time we found
• 36:37that if we reduced Selena,
• 36:40if we increase selenomethionine
• 36:41in the EGF receptor pathway,
• 36:43we drive activity of ERC which we know I did.
• 36:46I didn't show,
• 36:47but it's through Corkscrew S HP2,
• 36:49which happens to also be a a tyrosine
• 36:51phosphatase that's regulated
• 36:52by these lipid radicals.
• 36:54And so one of the things that's kind
• 36:56of coming out just from this initial
• 36:59one single compound that we focused on
• 37:01is maybe there's a vulnerability in in.
• 37:04In these the head and neck cancer cells
• 37:06for for a dependence on selenium,
• 37:08such that if a restriction diet that
• 37:11reduces the levels of selenium is used
• 37:13in conjunction with existing therapies,
• 37:16maybe they'll work better.
• 37:19So all of this is to say that the
• 37:21Y really matters for the students,
• 37:23and the way our scientific culture
• 37:25is set up right now we have a very
• 37:28high level principle investigator.
• 37:29It goes down, down,
• 37:30down depending on the level of training
• 37:32such that high school students are
• 37:34gifted with science and what we would
• 37:36like to do is change that so that the
• 37:38high school students come in with
• 37:40the science they already have that
• 37:41we figure out what those projects,
• 37:43those questions those hypotheses are,
• 37:46and matched them to a scientist who is also.
• 37:48Interested in the same thing and
• 37:50so so that it comes in more as a,
• 37:53you know, appear kind of attack on
• 37:56the same problem and so one of the
• 37:59things I really want to say is that
• 38:00the culture matters and so this is
• 38:02a an image of a boardroom from Time
• 38:04magazine from a little while ago
• 38:06where you can see the top guys are are
• 38:09all up here talking down here to the
• 38:12diversity equity inclusion officers
• 38:13who are supposed to be the ones who
• 38:15are focused on changing the culture,
• 38:18but instead they're being lectured on.
• 38:19This is our culture.
• 38:21And so one of the things that's really
• 38:23important is to consider whether
• 38:25this is your lab meeting, right?
• 38:26If this is your lab meeting and you're
• 38:28not considering the ideas of the people
• 38:30down here at this end of the table,
• 38:32then that's something that's
• 38:34really time to change.
• 38:36Finally,
• 38:36one of the things that's really our job
• 38:39if we take underrepresented students
• 38:40into our lab is to ensure their safety.
• 38:43You need to be the shield against
• 38:46the systemic racism that's coming
• 38:48at them from every direction,
• 38:50every minute of every day so that
• 38:52they can run behind you in a way
• 38:54that they can thrive and bring
• 38:56these new ideas into biomedicine.
• 38:58And finally,
• 38:58like I just want to share my own
• 39:00experience that the way these
• 39:02students think has completely
• 39:04changed the way I think about an
• 39:06important scientific question.
• 39:07Such that the biology,
• 39:09the environment,
• 39:10and the lifestyle all have to be
• 39:12considered so that we can really
• 39:13address particularly health disparities
• 39:15in cancer and other diseases.
• 39:18So I just want to leave you with
• 39:21with our group our crew from
• 39:232019 remember their faces.
• 39:25This is the future of Cancer Research.
• 39:28Isabella,
• 39:29here on the right side is just
• 39:31got accepted to a Yale summer
• 39:34program and she's considering that,
• 39:36and I think 14 other other programs so,
• 39:39so we'll see whether she comes.
• 39:41So we've had a bunch of funding,
• 39:43a lots,
• 39:44lots of support that we're
• 39:45particularly excited about.
• 39:46A recent partnership with
• 39:48the American Cancer Society.
• 39:49For the E close programs to
• 39:51support 300 young ladies doing
• 39:53Cancer Research this summer,
• 39:55and the team is amazing,
• 39:57I already mentioned Dara.
• 39:58I have my lab who's who supports all
• 40:01the students summer learning and a
• 40:04whole bunch of foxchase mentors.
• 40:07Yeah, so that's it. Thank you.
• 40:14Thank you so much, Alana.
• 40:16I'd like to ask folks to put
• 40:18questions into the chat,
• 40:20and if you don't I can start off with one.
• 40:24If that's OK with you, then maybe Barbara,
• 40:25I'm sure has questions.
• 40:27So First off that was.
• 40:28That was a fascinating presentation in a
• 40:30real Tour de force that congratulations,
• 40:33a lot of questions about the nuts and bolts.
• 40:35So how do you fund this?
• 40:38How do you channel hundreds of
• 40:40high school students in 220
• 40:43labs at best at Fox Chase?
• 40:46Right,
• 40:47we don't. We can't write.
• 40:49You can't do that. You can't have 2000.
• 40:52I mean, we're we're actually hoping to
• 40:54reach 10,000 students a year by next year,
• 40:56and there's no way that we can put each
• 40:58and every one of those students into a lab.
• 40:59It's just not possible,
• 41:00and so that's what we're trying to flip.
• 41:02So when COVID-19 happened,
• 41:04it became unambiguous that
• 41:06students couldn't come to the lab.
• 41:07And So what we did was we created a hybrid
• 41:10program where we create labs in a box,
• 41:13and we mail them to the students
• 41:15who create the lab in their house.
• 41:17And so, because fruit flies are safe,
• 41:19the dietary supplements are over the counter.
• 41:22Everything that they research
• 41:23is over the counter.
• 41:25That doesn't mean it's safe,
• 41:26but that just means it's legal
• 41:28for them to investigate,
• 41:30and so they they do all of
• 41:32the research in their homes.
• 41:33And so all of the initial.
• 41:36Initial data collection and
• 41:38analysis is is done in a way where
• 41:40we don't actually need any space,
• 41:42so we also train teachers.
• 41:44We have, I think 32 now teacher partners,
• 41:48each training about 100 students a year,
• 41:50and so the teachers now we just we
• 41:54got an award that I don't think
• 41:56I'm allowed to say what it is.
• 41:57But it's really big and exciting.
• 41:59That's gonna pay for building of Eclose
• 42:02Labs in 10 Philadelphia schools this year.
• 42:06And so now the schools will.
• 42:07We each have a fully equipped lab,
• 42:09just like the clothes lab for the
• 42:11students to do the work there.
• 42:13Yeah, so.
• 42:14So yeah.
• 42:14So and then the other thing we did was
• 42:17make it very inexpensive so dietary
• 42:19supplements don't cost very much and
• 42:21flies cost almost nothing and so the
• 42:23cost for for each participant once
• 42:26they have the lab setup is only $15 a kid.
• 42:29So so far we've been able to to do that.
• 42:33The primary driver of the revenue
• 42:34right now and the fund raising is that
• 42:37universities are sponsoring these programs.
• 42:39Everybody sort of wants well trained,
• 42:43underrepresented students to come to
• 42:44their school and so they are paying
• 42:47for us to run the programs for them.
• 42:49Which is,
• 42:49I mean,
• 42:50how could it get better right as
• 42:52a partnership like like we help
• 42:53you get your students ready and
• 42:55and you can get the funding.
• 42:56So so that's how it's been so far.
• 42:59But yeah, funding is always, you know.
• 43:02And then the so most of those
• 43:04Western blots being done in the
• 43:06echoes lab, and I presume that's
• 43:07a physical lab inside Fox Chase.
• 43:09No. So the western blots are done
• 43:11by the students who stay in the
• 43:13summer for the independent research.
• 43:14They get matched into the labs.
• 43:16We we have too many Westerns to
• 43:18do for that to remain feasible,
• 43:20and so last summer we developed a dot
• 43:22blot protocol which I should have put in.
• 43:25They were a little ugly and they
• 43:26weren't related to the projects I was
• 43:28talking about like, but but it works.
• 43:30So so you can do Erk,
• 43:32Erk dot blots that give you the same
• 43:34answer that you get on a Western and
• 43:36you can do them just by pipetting onto
• 43:38a membrane in a high school classroom.
• 43:41And so, so that's what we're sort of doing,
• 43:43is trying to figure out how to kind of.
• 43:45Actually, we could call it kicking
• 43:47at old school, like how?
• 43:48How do we do things before we
• 43:50could do all these fancy things?
• 43:51And then we're bringing those back with
• 43:53the idea that the professional labs
• 43:55will then confirm confirm the results.
• 44:00Barb, Yep.
• 44:02So a lot of amazing work and
• 44:06to touch so many lives it's
• 44:09it's just very inspirational.
• 44:12It's sort of like the the
• 44:13why question, but if you could take
• 44:15us back to when you started this.
• 44:19How did you get the Philadelphia Public
• 44:21Schools to let you in?
• 44:23And were there particular
• 44:25challenges in the beginning that?
• 44:27That if you knew now what you if you knew,
• 44:31then what you knew now,
• 44:32you would have structured a little
• 44:35differently in the beginning.
• 44:35Or how did it? How did it get
• 44:37off the ground to the scale?
• 44:39Yeah, so it it did end, right?
• 44:41We we started with 15 students.
• 44:43Our initial intention was eight because
• 44:45one of the reasons I went to Fox Chase was
• 44:47because they had a high school program.
• 44:49I participated in a program called
• 44:51Project Success when I was a grad student
• 44:53at Harvard and and Ben Neal's lab.
• 44:55And my student was.
• 44:58So extraordinarily smart and
• 45:00so extraordinarily unprepared.
• 45:02And so we spent the whole summer
• 45:04doing a lot of stuff.
• 45:05It it just became very clear that if
• 45:07a student like her instead of getting
• 45:09dropped into a lab like Ben's lab had
• 45:11had a training experience ahead of time,
• 45:14so that she would know how to measure,
• 45:16like know what a gram was,
• 45:18that it would be much different.
• 45:19So I knew that that she's now a chief
• 45:22attending at CHOP in Philadelphia.
• 45:25So extraordinary success.
• 45:26And and I know her and she has
• 45:29two little kids and it's amazing,
• 45:31but but it transformed me a lot more
• 45:33than it did hurt like like this is
• 45:35something where I can put this tiny
• 45:37little bit of effort into this and it
• 45:39can change somebody's whole family's life.
• 45:41So I knew that if I ever got a faculty job,
• 45:43I would want to create a
• 45:45training program ahead of time.
• 45:46So our first year we we trained 15 students.
• 45:49Most of them were not actually
• 45:52underrepresented from Philadelphia.
• 45:53It took us a couple years to figure out
• 45:55that Philly students weren't applying
• 45:56because they didn't think they could compete.
• 45:58With suburban kids,
• 45:59so we created a Philadelphia only section,
• 46:02and since then it's just been exploding.
• 46:04And then it's actually Dara who
• 46:06got into the Philly school system
• 46:08by her connections with teachers.
• 46:09So she was a teacher in the
• 46:12Philadelphia school system before she
• 46:13was a Community College professor.
• 46:15And so she just used those connections
• 46:17and we started getting in.
• 46:18We're not actually throughout
• 46:20the Philadelphia school system,
• 46:21yet we still partner with individual
• 46:24teachers,
• 46:24the inner City Schools are so
• 46:26oppressive to try to get into,
• 46:29and they don't have any money.
• 46:30To pay for STEM so.
• 46:32So we've just accepted that that's
• 46:34our responsibility,
• 46:35and yeah,
• 46:35so now people at you close are
• 46:38writing these grants to to to make
• 46:41sure that our Philly students
• 46:42are our highest priority.
• 46:45Atlanta can tell us a little more
• 46:46about E close. How big is it?
• 46:49How many people work there?
• 46:50How do they relate to Fox Chase?
• 46:53So you close is separate from Fox Chase.
• 46:56It's a separate nonprofit foxchase.
• 46:59Like I said is pretty small and so to run
• 47:01a nationwide program with 10s of thousands
• 47:04of students a year is not something
• 47:07that's that's within that capacity.
• 47:09So so we created it as a separate
• 47:12nonprofit almost our third
• 47:13year anniversary is coming up.
• 47:15We have 21 employees,
• 47:18all of them are part time.
• 47:21Third of them are instructors.
• 47:23A third of them are scientific
• 47:24technicians who build the kits and and
• 47:26and set up some of the experiments
• 47:29depending on what the program is,
• 47:31and then the the rest are.
• 47:34You know, I'm a volunteer,
• 47:35so I just said total volunteer.
• 47:39Yeah, so it's, uh, we're in 14 U.S.
• 47:42states now we have 11 university sponsors,
• 47:46including seven comprehensive cancer centers,
• 47:49the American Cancer Society
• 47:51sponsoring that huge program,
• 47:52and we have programs ranging all
• 47:54the way from 5th grade through
• 47:56through adults interested in
• 47:58transitioning into biomedical careers.
• 48:00So it's a it's a very rapidly,
• 48:03rapidly growing thing,
• 48:05and I think the COVID pandemic when
• 48:08nobody could actually do any science.
• 48:11With you know all of a sudden they're like,
• 48:13wait.
• 48:13I heard about these people
• 48:15who started this thing,
• 48:16so I'm in the equals lab now.
• 48:18It's 500 square feet and it's you know,
• 48:21we'll we'll grow as we grow.
• 48:25There's a question from the
• 48:26audience from Doctor Rose,
• 48:28so are these other resources to help
• 48:30these young people get into college,
• 48:32pay for college, and do you
• 48:34find these issues are barriers?
• 48:37So we don't have those resources.
• 48:39Uhm, like I said, we don't actually
• 48:41even have full time employees yet
• 48:44that that's that's something that.
• 48:48Yeah, I'm not.
• 48:49I'm not sure that we will get there
• 48:51because most of our students end
• 48:52up getting full ride scholarships,
• 48:54so our biggest sending schools at this
• 48:56point are University of Pennsylvania,
• 48:58which has hosted 32 of our senior
• 49:01level students and I don't think
• 49:04any of them has paid and our second
• 49:06biggest sendings will now is MIT.
• 49:09We also have a lot of students at
• 49:12Pitt and Drexel and Temple and I
• 49:14don't think any single one of our
• 49:16students who've gone to Temple has
• 49:18not been assigned scholar, which is.
• 49:20For four year scholarship with
• 49:22room and board,
• 49:23the whole the whole 9 yards.
• 49:25And so I think the unusual nature
• 49:29of having this kind of research
• 49:31experience a personal statement
• 49:34that's talking about how discussing
• 49:36your personal why the person that
• 49:38you did this for and how you are
• 49:41going to bring together all of the
• 49:43interest that you gained from this
• 49:45program into creating a project is
• 49:47going to be transformative is pretty.
• 49:49It's pretty well received by.
• 49:51By colleges and universities.
• 49:53So far so so that may be something where
• 49:56there's another nonprofit that's doing that,
• 49:58like providing scholarships and
• 49:59things we would love to partner.
• 50:01Like I said, it closes a hub.
• 50:03We want to kind of drop down the barriers
• 50:05of competition so we don't really.
• 50:08You know,
• 50:08I've had a lot of people in fly land say,
• 50:11oh,
• 50:11we'll just replicate your program
• 50:12like that's great,
• 50:13but now we're your date is
• 50:14gonna be over there.
• 50:15Our date is what's the point like
• 50:17why don't we do this together so so
• 50:19that's one of the main things we're
• 50:21working on this year is how to.
• 50:23Collect the data so that if somebody does
• 50:25replicate the program just on their own,
• 50:28how is it that they can contribute to
• 50:30the database so that all of us can,
• 50:32you know,
• 50:32use this kind of screening data
• 50:34for for advancement of science.
• 50:37And one of the
• 50:37things that struck me in your talk
• 50:39was that you said multiple times
• 50:41the students decided to do this,
• 50:43that or the other the student
• 50:45was interested in this question.
• 50:47So essentially none of us gets
• 50:49to really choose what we decide
• 50:51to do in science all the time.
• 50:54You have to have funding.
• 50:55It has to be practical and feasible
• 50:57and so on. So when a student.
• 51:02Their shows interest in something.
• 51:03How do you channel them to a lab that
• 51:06might actually have the expertise?
• 51:08See that you don't have endless
• 51:10labs approx chase
• 51:11right? So this this is our that that's
• 51:13like our newest newest thing. So the 1st.
• 51:17Four years, maybe five years of the
• 51:20program was really just my thing.
• 51:22Like let's do EGM perceptor because you know,
• 51:24we had to figure out how to do it all.
• 51:27Does the data even mean
• 51:28anything like thank heavens,
• 51:29the people counting is really,
• 51:30really really significant and important.
• 51:33So, so we spent those five
• 51:34years just doing my thing.
• 51:36So in 2017 we started getting
• 51:37kids bringing in bags of like my
• 51:40mom's eating this and then that's
• 51:42when that started to change.
• 51:43And so it's really only in the past
• 51:46two years where we're trying to.
• 51:48Bring together Foxchase faculty who
• 51:50do specific things so we have behaved
• 51:54social behavioral researcher Carolyn Fang,
• 51:56who's extremely interested
• 51:58in medical mistrust.
• 51:59Who was more than happy to
• 52:01host Nicole in doing this?
• 52:02This project that she's doing and
• 52:04then together we got this small
• 52:06foundation grant for five more
• 52:07students to continue that work.
• 52:09So Caroline, will,
• 52:11you know,
• 52:12support them and developing
• 52:14educational interventions specifically
• 52:15designed for the communities of
• 52:18the participating five members?
• 52:19Of that of that research group,
• 52:21and then Jeff just happened to
• 52:23work on Ferroptosis and we landed
• 52:25on iron and acetaminophen, right?
• 52:27So so so far, it's like coming together.
• 52:29Last summer we had seven students.
• 52:31Everyone from a different cultural
• 52:33background who all were interested
• 52:35in BRCA driven breast cancer.
• 52:37All of them had a family member.
• 52:39We have another group that's
• 52:41interested in beta thalassemia,
• 52:43so a number of different again cultural
• 52:46groups that were interested in that.
• 52:48And so right.
• 52:49This is why.
• 52:50By the concept of eclose is going to
• 52:52become more and more and more important,
• 52:54especially with university sponsors,
• 52:55because where am I gonna send the
• 52:58kids I I'm already way overwhelmed.
• 53:00Like Oh my gosh,
• 53:01I can't think about all of these
• 53:03projects all at the same time,
• 53:05and so that's what we sort of need.
• 53:07And so we're kind of thinking about
• 53:10creating like a fast pitch competition.
• 53:13That's a video based thing
• 53:14where every student would like
• 53:16hold up their phone and go.
• 53:17Oh,
• 53:17and this is the project
• 53:19I'm really excited about.
• 53:19And then the scientists
• 53:21would just go through.
• 53:22You know no more than 30 seconds to a
• 53:24minute pitch and say that student is
• 53:26interested in what I'm interested in.
• 53:28So do you see what I mean?
• 53:29Like we're hoping to kind of like
• 53:31change it so that the students
• 53:33actually can go into a lab.
• 53:35That celebrates their interests.
• 53:36We also I forgot to say we have a
• 53:39partnership with Penn Medicine that
• 53:40takes a number of our students each
• 53:42year and they have they're much bigger,
• 53:44so they they have more capacity.
• 53:49Wow, that's an amazing undertaking.
• 53:51The whole thing. But what percent
• 53:52of your time do you spend on this?
• 53:54Just one last question. Unless Barbara
• 53:56I'm officially allowed to spend one
• 53:57day a week, that's what I spent.
• 54:00OK, we won porcian that yeah.
• 54:04Burp. Any closing coming up?
• 54:07You know I, I just want to say
• 54:11again that the the creativity and
• 54:13the the way you've leveraged what
• 54:16started out as small experiences to.
• 54:18To extend to so many people
• 54:20and and also you know.
• 54:22So I know that at Yale,
• 54:24over 50% of our first generation
• 54:28and underrepresented undergraduates
• 54:30when they show up as first years.
• 54:33Say that they want a major in
• 54:35STEM and the attrition is,
• 54:37as you said,
• 54:38over 70% of of them don't end
• 54:40up graduating in a stem.
• 54:44Programs or major.
• 54:45So the you know the fact that
• 54:47you are seeing 100% retention in
• 54:49STEM and that your medical school
• 54:52PhD balance because you know,
• 54:54we're also aware that minority communities
• 54:57are more familiar with the physician
• 55:00as a role model than the scientist.
• 55:02I think those just they they said
• 55:04a very high bar for everybody
• 55:06else who works in this space.
• 55:07It's amazing.
• 55:08Well yeah, I mean we,
• 55:09you know we could just help you like that.
• 55:11That's one of the things
• 55:12that we I actually met.
• 55:14Tony Koloski at this huge professors
• 55:17competition that we were both finalists
• 55:19there and the goal behind that was
• 55:22to create undergraduate a first year
• 55:26undergraduate semester of doing this.
• 55:28Like doing the program that we
• 55:30designed and so that students
• 55:31wouldn't go into that weed out class.
• 55:33Because every school has a weed out
• 55:36class which I cannot comprehend
• 55:38right at Temple at Temple,
• 55:40which was the partner they
• 55:41say we give them chemistry.
• 55:43We failed.
• 55:4470% of the students and this is
• 55:46like a we did a good job.
• 55:47We failed 70% out and so why would
• 55:49you recruit students who are already
• 55:51vulnerable not based on their own fault,
• 55:54but because of the challenges of an
• 55:56inner city public education and then
• 55:58fail them out like that's basically.
• 56:00You know it's it's so unfair
• 56:02it's basically taking any little
• 56:04tiny step on the rug that you
• 56:05had and yanking it right out.
• 56:07So,
• 56:07so that's what we would be dreaming
• 56:10of having in the future is to be
• 56:12able to work with each and every
• 56:14school to say what's the most
• 56:16important research that you're doing?
• 56:18How do we create interdisciplinary groups to,
• 56:21you know,
• 56:22have a student who's interested in
• 56:23public health together with a student
• 56:25who's interested in chemistry biology.
• 56:27Do you see what I mean to to basically
• 56:29create those kind of program project
• 56:32groups from students as their
• 56:34very first research experience?
• 56:36That's what we really want to do.
• 56:39It's amazing,
• 56:40thank you so much. That was amazing.
• 56:43Incredibly inspiring. Thanks for
• 56:44taking the time to talk to us today.
• 56:47Thanks, thanks everybody.
• 56:49If you have questions,
• 56:51you can find me. Alana Fox Chase.
• 56:54OK.