NINR Director's Lecture – Dr. Taylor

[music playing] >> Patricia Grady: And welcome to our second NINR Director’s Lecture of the year We’re very pleased to have you here this afternoon, and also admiring of the fact that you have braved the weather out there And some of you have flown in from around the country, and that’s always tricky in this area when the weather is like this We — several times a year, we have the NINR Director’s Lecture, and it is an opportunity for us to bring to you — before you people who are experts in the areas of science that we support And they — we have the opportunity to listen to a program of research over an extended period of time, as opposed to single-lecture episodes And so, it is an opportunity for us to see how the science has grown over time It’s also an opportunity to get a window into the future, where the science is going from this point on And it is an opportunity to network with people across the campus and across the country This lecture will be taped — is being videotaped and will be archived on our YouTube channel, so that you, when you go back to your respective places and talk about how good it was, people can then look it up and see it for themselves It also — that makes it available for classes and for students as well, which we think is a real advantage And it helps us, as well, because it’s a really encapsulated and succinct way for us to talk about the importance of the science So, let me just say that today, we are very proud of our programs across the board in symptom science, self-management, wellness, and end-of-life and palliative care And one of the dominant threads across all of these, that’s an integral part, is the attention to cultural interventions and health disparities And so, we’re particularly pleased that Jackie is with us today to be able to address that important concept that is cross-cutting across the entire portfolio of research Regarding that is also an opportunity to showcase some of the important work that we do with communities In order to be able to address health disparities, it’s really important to be connected to communities locally and across the globe, as well And so, the community connections, the inter-disciplinary approaches, are particularly essential to this type of research So, we’re really excited that Jackie Taylor can be with us today Let me just say a few words about her I know you have her bio and she’s — as most of our speakers, request that I don’t make it too long, so — and I won’t cut into her time too much But Jacquelyn Taylor is respected across the country and increasingly across the globe for her work, which is focused on, interestingly, the interaction of omics and social factors that contribute to health disparities for those with common chronic conditions, in particular across under-represented minority populations This is something that she has dedicated her entire research career to Now, her long-term goals are to develop interventions to reduce and prevent omic environmental risks associated with health disparities in diverse populations across the lifespan Her research includes and inter -generational hypertension study examining the effects of genomic and environmental interactions of perceived racism and discrimination, parenting stress, and maternal — mental health on blood pressure in African American mothers and their young children; she is also in — speaking of community activities — she is also investigating the genomics of lead poisoning in Flint, Michigan, looking at ways in which the lead exposure, along with genetic and psychological factors like stress, can influence high blood pressure among the residents of Flint Very timely and important study which hopefully will give us a window into how to handle these kinds of health crises in the future So, Dr. Taylor is an Associate Professor and the Inaugural Vernice D. Ferguson Endowed Professor in Health Equality at the Rory Meyers College of Nursing at NYU For those of you who have historical roots here, you will know — recall that Vernice Ferguson was very important in the clinical center for her work with the clinical center and with the nursing department, as well as her work in the public health service So, Vernice is very important to us, as well So, it’s like a double pleasure to have Jackie come and also to have the Vernice Ferguson Endowed Professor here

She also, before coming to NYU, served as a tenured faculty and Associate Dean of Diversity Inclusion at the Yale University School of Nursing She’s received a number of honors and belongs to several prestigious associations of nursing, but the one I really want to mention in particular, to single out, is the Presidential Early Career Award for Scientists and Engineers, otherwise known as the PECASE award This is the highest honor bestowed by the U.S. government to outstanding scientists and engineers in the early stages of their independent research careers She is the fourth nurse to receive this award since its inception, which is about 15 years ago So, this is a really important honor that Jackie has received And so, we are particularly proud of all of her activities, but especially excited about that one So, we look forward to hearing her speak this afternoon on Hypertension Genomics in Black Families: A Tale of Three Studies and Counting So, after about 30 minutes, Dr. Taylor will moderate a question and answer session So, please join me in welcoming Jackie today [applause] >> Jacquelyn Taylor: Thank you so much [applause] Well, thank you so much It’s a pleasure to be here with you all and thank you for the lovely introduction So, when I was asked to come and speak with you all today, I thought it would be important to give you some context of where things began for me How small studies really helped shape the work that I do today, and how it helped move, you know, the science that I’m doing forward, and what I’m doing today, and what I plan to do in the future So, I’m going to start by just giving you a little bit about my educational background I started out at Wayne State University in the baccalaureate program in nursing And during the entire time that I was in nursing school, I spent all four, almost five years as a laboratory technician in a physiology laboratory, doing work with rat models and looking at contractility of the vessels, doing work with vascular smooth muscle cells And people always asked me, “How did you get involved with doing basic science research?” And it was very serendipitous because I was just a poor student that started college that needed a job, so I went to the guidance counselor at Wayne State University and I said, you know, “I’m looking for a job, what can I do?” And the guidance counselor, she must have been having a rough day But I was 18 years old I didn’t realize that she was being — she was very annoyed with me [laughter] She said, “What do you want to do?” And I said, “Well, I’m very interested in hypertension This is a problem in my community My father has hypertension He’s had a stroke I want to really look into this more, particularly in the black community.” And she said, “Well, you really need to go and talk to the department chair that’s at the medical school in the department of physiology.” I didn’t know what a department chair was I didn’t know that you should probably make an appointment to talk to the department chair [laughter] And I said, “Well, who is that person?” I really thought she was being helpful And she said, “Well, it’s Dr. Dunbar.” And so, I went over to the medical school [laughter] And messaged Dr. Dunbar And I first called, and his assistant answered the phone, and I, you know, told them who I was, and I wanted to speak to Dr. Dunbar about, you know, doing some work in hypertension And I can just imagine on the other side of the phone, the laughter [laughter] Like, “Who is this person?” But he took pity on me and I worked in one of his laboratories for the entire time that I was an undergrad And that really helped to shape, you know, my knowledge in physiology and doing bench science, and how I could build on the work that I was doing in the laboratory and make that translatable to clinical practice Now, back then, we didn’t have the term “clinical translational science” or “bench to bedside.” I just saw it as nursing So, then I went on to do my master’s work at Wayne State and I enrolled in the master’s program, and my master’s advisor was Dr. Candace Covington And I distinctly remember talking with her about applying to the master’s program, and she, in her very southern accent, said, “Why aren’t you applying to the Ph.D. program?” And I said, “Well, you know, I was told that you had to work so many years before you could apply to the Ph.D. program.” She said, “Who told you that?” And she took that master’s application away from me — [laughter] — and brought me the Ph.D. application And she said, “Here, you can fill it out right now.” Because she was in her office working on her grant, and I was very [laughs] — I was very agreeable, so I applied to the master’s Ph.D program at Wayne State and was accepted So, I ended up doing my master’s work with her, and then my Ph.D

thesis advisor was Dr. Olivia Washington And at the time, she was funded by NINR, with a grant where she was doing blood pressure telemonitoring So, I was able to do my doctoral work through a minority supplement on her R01 And then, as I continued my education, I wanted to do more across-the-lifespan work So, I felt very comfortable with my knowledge in pediatric populations and, you know, young children, but I wasn’t quite sure about the older population So, I decided to do a post-doc in gerontology, so that I could expand the across-the-lifespan work that I wanted to do And so, my mentors for my post-doc were Dr. Peter Lichtenberg and Dr. James Jackson Peter Lichtenberg was at Wayne State, but they had a joint grant through National Institute on Aging for the post-doc in urban health aging And then, I quickly found out that the genetics work that I was doing required a lot more advanced statistics that I was trained for in my doctoral program So, I applied to a program through Washington University in St. Louis, which was an NHLBI-funded R25 [phonetic sp] — which is now the PRIDE [phonetic sp] program; it was the SIPC [phonetic sp] program way back then — so that I could advance my knowledge in advanced statistical analysis and, specifically, in cardiovascular genetic epidemiology My mentors there were Dr. D.C Rao and Dr. Victor Davila-Roman And I put all of these pictures here so that you can get a sense of the type of mentorship that I received and the diversity — not just racial and ethnic diversity, but diversity across disciplines I started off with a physiology mentor, then have my nursing mentors, a gerontologist, genetics, a physician, and a social scientist So, I really started out and always had a sense of working with people across disciplines And then, some of my work background: I have worked, obviously, as a registered nurse I have worked as a clinical nursing instructor, pediatric clinical nursing instructor As a nurse practitioner — I really loved this job It was a mobile clinic that we had in Detroit I did everything, from seeing the patients to driving the van — [laughter] — to transporting all the equipment These are Detroit Lions football players — I don’t know who they are [laughter] They could be very important people and excellent players, but I just don’t know [laughs] But the mobile clinic was funded by a private grant through Edsel Ford, who is the owner of Ford Motor Company, and the Detroit Lions And so, one of the schools that we provided care to was the Detroit Lions Academy So, that’s why you see the football players there And so, a lot of the work that I do stemmed from my clinical experiences, the work that I did in the communities across Detroit I also had, once I completed all of my work, my first academic appointment on the tenure track was at the University of Michigan, where Ada Sue Hinshaw, who needs no introduction here, I’m sure, took a chance and hired me [laughs] as an assistant professor And I’m so happy that she did She remains one of my mentors I just saw her about a month ago at Wayne State University at the Urban Health Conference, along with Dr. Ann Cashim [phonetic sp] And we were able to catch up there Another mentor that I had at the University of Michigan was Dr. Sharon Kardia She was my K02 [phonetic sp] mentor on work that I was doing in cardiovascular genetics, and she is a genetic epidemiologist at the School of Public Health at the University of Michigan After that, I spent quite some time at Yale — nine years as Assistant Professor, and then became tenured, and actually lived in the dormitory as a resident fellow for three and a half years, mentoring undergraduate students Which — that was a lot of fun, I must admit And then I went on to become Associate Dean of Diversity and Inclusion at the Yale School of Nursing I also spent a couple of years at MIT, as a visiting professor through their Martin Luther King Jr. program in their biology department, because I wanted to expand some of the omics work that I was doing, and actually look at whole genome sequencing, particularly in minority populations So, my mentor there was Dr. David Housman And now, I am currently at the Rory Meyers College of Nursing at New York University Dean is Eileen Sullivan-Marx,

who, she doesn’t know it yet, but she will become my mentor [laughter] So, watch out. [laughs] So, again, vast array of different mentors and different influences of the type of work that I do So, I’m going to get right into it as not to waste time and talk to you about a few of the smaller studies that I’ve done The first one being a study that was funded by NIA — a P20 pilot award in NHLBIK Then, a replication study in West Africa, and then another study funded by the Robert Wood Johnson Foundation, which I think were all instrumental in building the portfolio that I currently have, to obtain the funding for the work that I do that’s supported by National Institute for Nursing Research So, basic understanding of genetics: I won’t go through this because I know this audience knows a lot about genetics and base pairs and SNPs and single nucleotide polymorphisms But I’m going to talk a lot about SNPs that I looked at in some of these studies, and how they are associated or were associated with hypertension, particularly in black populations So, the very first study, as I mentioned, was funded by a P20 pilot, which, you may think, you know, a little pilot grant, it’s, you know, not that much money But for a junior faculty just starting out, it means absolutely everything And so, in this study, I wanted to look at multiple generations of African American women and hypertension susceptibility genes And I just wanted to do a descriptive study, and I wanted to see if I could identify SNPs that were associated with high blood pressure even in a younger generation prior to development of the disease So, why hypertension? Why look at this, and why black women? Well, we know that African American women in particular have the highest incidence and prevalence of hypertension of any ethnic or gender group in the United States And in particular at the time, Detroit had the second highest rates of hypertension in the United States, just behind Memphis What we know about hypertension: we know that lifestyle factors contribute to hypertension We also know that genetic inheritance has been associated with hypertension But at the time, I wanted to look at the combination of these two factors, and what the interaction of these two factors — how that would influence blood pressure among multiple generations So, this small study was just descriptive, and we wanted to determine if genomic risks for hypertension could be detected prior to phenotypic expression of the disease And in this study, we had 180 participants, so, 60 triads of African Americans across Detroit that were recruited At the time, we only looked at four SNPs This was before, you know, genome-wide association studies were very prevalent And we looked at, you know, just using a descriptive design These were the eligibility criteria The one eligibility criteria that I want to point out is that all three members must be together at the same time for data collection, because that was not in there when I first started this study And if you know anything about Detroit, you know that you can drive for about an hour and still be in Detroit It is a very large city, and if you’re trying to track down three different people at three different times, it will take you forever So, what I learned very quickly was just to talk to the grandmother, and if the grandmother said, “They will all be at my house at this time,” I didn’t have to check with anyone else The grandmother — she made it happen So, another thing that I did, in terms of recruitment strategies for these participants: I really looked toward all of the opportunities that I had prior to starting my faculty position I utilized the University of Michigan women’s health registry I knew there was a health registry — participant research pool at the Institute of Gerontology at Wayne State, where I had completed my post-doc I posted study flyers at various places: grocery stores, hair salons, and so on And then, it dawned on me, because I’m a member of a historically black sorority, Alpha Kappa Alpha Sorority, Incorporated And we have meetings every month And typically, women join the sorority that their mothers were a part of or their grandmothers were a part of And at these meetings, I noticed that there were multiple generations of black women in the room, every single month So, this particular sorority allowed me to recruit

from various chapters throughout Michigan And that really helped out, as well And then, social networks of enrolled participants People are very interested in how I was able to enroll African Americans into genetic studies, so I went on to publish this article in the Journal of Transcultural Nursing, just to talk about this particular topic So, these were the measures that we collected We did buccal swab, because we were only looking at four SNPs at the time We collected all these measures, but 24-hour food recall was of most interest to me for several reasons, and I’ll get to it But it was so much fun to collect this data I thought it was going to be very cumbersome, that people wouldn’t tell me exactly what they ate, that they weren’t going to be truthful People told me everything [laughter] And then, if it was a recipe or if they made something at home — I learned so many great recipes And then, I would, you know, go and collect data, people would feed me It was awesome [laughter] It was so much fun So, here are the demographics for the sample Of the grandmothers, 73 percent were diagnosed with hypertension And, as you remember from the earlier slides, the rates for African American women is about 44 percent in the United States for diagnosis of hypertension This is way higher For the middle generation, 42 percent were diagnosed with hypertension, and even the granddaughters, about 12 percent had been diagnosed with hypertension And this is the age — the mean ages for those groups As you can see here, this is the mean of blood pressures 146 over 82 for grandmothers, 134 over 83 for mothers, and 125 over 79 So, not too bad, but you have to remember that these — the people that were diagnosed with hypertension were being controlled with anti-hypertensive medication We also looked at pulse pressure, and we know that a normal pulse pressure is 40 millimeters of mercury, and we can see that the pulse pressure is way outside of the normal limits Body mass index: in this population in Detroit, you can see, among all three generations, well above the normal weight limit In particular, the grandmothers and the mothers were in the obese category, while the granddaughters were in the overweight category We also looked at percent body fat, because we know looking at BMI in black populations can be controversial So, you also want to look at another measure of body composition And as you can see here, percent body fat was well outside of the normal limits for healthy body fat for women And here, we just looked at correlation of blood pressure and the four SNPs, and we found that all four SNPs were significantly correlated with increase in systolic blood pressure, which we thought we would find But we also found that pulse pressure was significantly correlated with two of the SNPs We published this work in Biological Research for Nursing, and we moved on to do statistical analyses for interaction And this was why I needed to do additional training in advanced statistical analysis, because it wasn’t just doing a regression analysis We had to do multi-variant linear regression models, we had to do linear mix models, multi-variant mix models, and we were looking at sodium intake because I was very interested in diet And then, we had to correct for anti-hypertensive medication use Once we did all of that, one SNP was significant for interaction with dietary sodium intake in predicting increases in systolic blood pressure So, the — but, what was interesting was that the T allele was found to be protective, and resulted in lower systolic blood pressure, even when people consumed greater amounts of sodium than the daily recommended value But the C allele was found to be the risk allele for increases in systolic blood pressure So, what did I learn from this small study? Well, we learned that chromosome two and, in particular, the sodium bicarbonate transport gene, was a harbinger for hypertension, and the expression has been shown in all of these organs But surprisingly, the T [phonetic sp] genal type was protective against increases in blood pressure And we thought, “Well, maybe this could be due to some other factors, like body mass index or physical activity, and things like that,” and could we replicate this in another sample to see if our findings were valid So, this study just basically showed that it was feasible to enroll African Americans into an omics study, which people thought that I would have trouble doing

But I actually had more people that wanted to enroll in the study than I could enroll So, we had reached our enrollment goal and we had to close enrollment And the results were encouraging regarding the relationship between blood pressure and genetic polymorphism So, we were able to publish in several journals on this topic Journal of National Black Nurses Association, Biological Research for Nursing, and Journal of Transcultural Nursing, Journal of Pediatric Health Care, and in Hypertension So, one of the things we wanted to do was replicate in a similar sample to see if we could have similar findings But one of the reviewers — and I always call it “Reviewer Number Two,” is the one that just does not like anything that you do, right? [laughter] So, “Reviewer Number Two,” you know, you found this, it’s very interesting, but could you replicate this in a sample of blacks that are not overweight, have a healthy lifestyle, get a lot of physical activity and have healthy diets? I’m like, “Well, they probably wouldn’t have hypertension, right?” But if you’re making the case that, you know, there’s genetic underpinning, then, you know, maybe this could be true So, I talked with one of my mentors, Dr. James Jackson He said, “Well, go over and talk to some of the people over in anthropology.” And so, that’s exactly what I did I went and I talked with an anthropologist, and I said, “Do you know of any, you know, groups of African Americans or blacks that have trouble with hypertension but, you know, have healthy lifestyles and, you know, still have high blood pressure?” So, what I found was that the Dogon tribe in Mali, West Africa — they are a tribe that lives the same way they have lived since the early 1400’s They hunt and gather for food They are mostly underweight instead of overweight, but they still have issues with hypertension Now, what does that have to do with their relationship with people in Detroit? Well, we know that many African Americans have ancestral roots that were part of the trans-Atlantic slave trade And more than 39 percent of the 12 million slaves transported from West Africa to the Americas came from Mali, which is where this tribe is, and were members of the Dogon tribes And in the early 1800’s to 1900’s, nearly 90 percent of African Americans resided in slave-holding states in the south But during the great migration, between 1915 to 1930, many African American slave descendants relocated from southern states to northern states due to — for better employment opportunities For example, the big three auto makers, including my father He moved from South Carolina to Michigan to work for Ford Motor Company So, from 1910 to 1929, Detroit’s black population increased from 6,000 to 120,000, making Detroit a major northern migration destination for southern blacks So, that’s why Mali These are images of Mali in West Africa They still live in clay huts Again, they live the same way they’ve lived since the early 1400’s They are a polygamous society, very homogeneous genetic population, which is very exciting for someone that does genetics research They only marry within the seven tribes They hunt and gather for food The men can have as many wives as they can afford [laughter] The language is Dogon, so there’s not a written language It is an oral language, but the official language in West Africa is Bambara And as you can see, there’s no running water or electricity or sanitation There’s no golden arches; there’s no, “Have it your way.” [laughter] There’s none of that So, you are naturally controlling for diet and physical activity This is my free research assistant that came all the way to Mali, West Africa How do you get a free research assistant? You tell your husband you’re going to a polygamous society that can have as many wives as they can afford, and you walk away [laughter] Free research assistant [laughs] So, this is millet I didn’t know what it was until I went to Mali This is what they eat It’s a grain

They grow it and they pound it into a powder and they mix it with water So, very healthy diet They eat a lot of lamb and chicken and fish We stayed at a hotel in Mali, right outside of the Dogon tribes, but it was not by any means a hotel by American standards Again, no running water, no electricity And, we went to the hotel and you just ate whatever they had for that day, and they said, “Okay, we have chicken.” So, we said, “Okay, we’ll have chicken,” but then we heard them slaughtering the chicken And so, after that, we ate a lot of onion soup [laughter] Because we didn’t want to hear that But, as you can imagine, the IRB process was very lengthy, because we’re dealing with a group that has an oral language So, everything had to be translated from English to Bambara to Dogon And when we went to each one of the villages, we had to have a translator that knew English, Bambara, and Dogon, and could translate everything to English for us and back to Dogan for the chief And we met with the chief of each village, and once the chief gave his permission, then women were very open and willing to participate All consent was done verbally, and the inclusion criteria was the same as the Detroit women We had 199 people enrolled We did this in 10 days [laughs] It pays to have a free research assistant [laughter] And all of the samples came back to the States in good shape We only had two grandmothers that were excluded due to insufficient DNA sample for analysis We gave each participant $1 That was the most that the IRB would allow us to give, because that was equal to 500 central francs of Africa So, that was a lot of money to these participants We used the oral gene saliva sample because it would stand the extreme heat in West Africa We looked at six SNPs instead of four, because you know, as with any research, you have more SNPs that are found in the literature associated with high blood pressure And we were able to publish some of this work, as well, in Biological Research for Nursing We used the same statistical methods as before The only thing that we didn’t do is we did not correct for anti-hypertensive medication use, because none of these people were taking anti-hypertensive medications The local hospital was two hours away So, they had bigger problems than going to the hospital for anti-hypertensive medications We had people that died from malaria and other communicable diseases while we were there But as you can see here, this was the average age of the grandmothers, mothers, and granddaughters But I want to draw your attention here: 35 percent of the grandmothers had blood pressures that were diagnostic for hypertension, 10 percent of the mothers, and one and a half percent of the granddaughters met the criteria for hypertension But as you can see here, body mass index was starkly different than that of the African Americans And you can see, most of these women were in the either normal weight category or underweight category, whereas my Detroit sample, they were overweight or obese But we found the same gene that was significant for increases — the same SNP that was significant for increases in systolic blood pressure in Detroit as we did in this sample And that was the very first time a parallel sample of a study done in the United States and then controlling — naturally controlling for diet and physical activity in West Africa had been conducted So, we went on to publish this work, because the results were the same We did not find the protective T allele in the Dogon sample I’m still not really sure why it was protective in the Detroit sample and not in the Dogon sample, but we did not find that similarity So, again, this study informs providers that we can look at genetic underpinnings early in life, before — prior to phenotypic expression We were able to publish this work in several places: Biological Research for Nursing, Ethnicity and Disease, and Yale Journal of Biology and Medicine So, again, I thought I was pretty satisfied with the work we had done here, because you didn’t know what you were going to find in West Africa, and we could have just done this work and found nothing But “Reviewer Number Two.” Not necessarily of this article, [laughs] but “Reviewer Number Two” said, “That’s great, you know, you did this You replicated, you have the same findings, but could you replicate this in a large epidemiological sample of blacks?”

I’m like, “Are you kidding me?” [laughter] But it was a valid question, right? So, I went to one of my mentors that I had on the screen earlier, my mentor from Washington University in St. Louis And I talked to him — he was the director of the HyperGen study, part of the Family Blood Pressure Program And I said, “You know, if I’m able to get some funding, would I be able to gain access to the HyperGEN data set that has, you know, mothers and daughter, and all the mothers are hypertensive, all the offspring are not? Would I be able to access that data as a replication sample?” And he said, “Sure.” So, I put these images here because I applied to the Robert Wood Johnson Nurse Faculty Scholars Program to fund this project, where I could look at BMI’s internal environment and look at hypertension susceptibility genes using genome-wide association So, here in this study, I would be able to look at more than a million SNPs on each individual in both mothers and daughters And so, these people became my mentors throughout that program, and they need no introduction, but in case you don’t know, this is Dr. Jacquelyn Campbell at Johns Hopkins, Dr. Angela McBride, and Dr. Beverly Malone And they still, to this day, continue to mentor me in one way or another, and I’m very thankful for all of their support So, this is Dr. D.C. Rao from my other slide, from the beginning He is the Director of the HyperGen — the Data Coordinating Center at Washington University in St. Louis, and he was my mentor at — with the PRIDE program So, as part of this particular study, I was able to look at 868 African American mothers and 322 African American daughters There are less offspring because some of them were boys and, at this point, I was only interested in the mothers and daughters because the other studies were with mothers and daughters And these people were recruited from Forsyth County, North Carolina, and Birmingham, Alabama, as part of the Family Blood Pressure Program So, with the genome-wide association data, we had many controls that we looked at before we started analyses And so, once we looked at positional candidate genes known to have associations with hypertension, we only had 115 loci in mothers and 491 in daughters We excluded if the call rate was less than 90 percent, and if the minor allele frequency was less than five percent And this resulted in 436 SNPs in moms and 95 SNPs in daughters And we selected the positional candidate genes using these databases We did the exact same statistical analyses as before This is the breakdown of the mothers and daughters, and again, all the mothers in this sample were hypertensive All the daughters had never been diagnosed But as you can see here, blood pressure’s 134 over 74 and 116 over 69 But again, the mothers were controlled with anti-hypertensive medications But look at this BMI — it’s similar to what we found in the Detroit sample Both mothers and daughters in the obese category And this — these were the main effects that we saw with the SNPs in systolic and diastolic blood pressure We expected to find something because we had so many SNPs to examine, but what was so interesting was that we found these six SNPs that were significant for increases in systolic and diastolic blood pressure in these daughters that were not hypertensive When we did the SNP by BMI interaction, this one SNP continued to be significant, and we published that in Biological Research for Nursing So, this was the first time that this gene and SNP had been identified in undiagnosed African American girls as a risk factor for hypertension And this one was also located on chromosome two but was in a different gene And here is some information about this gene: it had been identified in hypertensive rats before and had been found in human testes and lung tissue But I think we can safely say it was restricted to lung tissue, since it was only women in the study [laughs] And this is what the mechanism of action is for this particular gene So, quickly, just a comparison of the three studies We found that chromosome two was a harbinger for hypertension in all three studies It was the same SNP in the same gene for the Detroit sample as with the West African sample, but a different gene and different SNP for the large epidemiological sample in HyperGen So, these consistent results among African American offspring and BMI interaction suggest that differences

in both systolic and diastolic blood pressure, respectively, depend on genetic underpinnings and other factors, like BMI, that is identifiable early in life I put this picture here because all of the work that I do is related to decreasing the risk or even eliminating the risk for cardiovascular compromises in younger generation, like their mothers and their grandmothers and in older generations This is a group of — we call them “The Ivy League Academy.” We bring them to Yale in the summer, just to show them that there are people out there doing research on people that look just like them and have — and that really care about their health So, more information about the CAPNI gene — CAPNI13 gene We were able to publish those results in scientific reports and in Biological Research for Nursing And now, we’re getting to what I’m doing now, and I’m mindful of the time So, now I’m currently funded by National Institute of Nursing Research, where I’m looking at the inter-generational impact of genetic and psychological factors on blood pressure, which we call the InterGEN study, for short We are currently almost completed with enrollment Our goal was to enroll 500 families We recruited from Head Start programs across Connecticut We are currently at 450 people enrolled And then, we follow them every six months for two years, and we collect genomic data We have whole genome — genome-wide association data using the MEGA array [phonetic sp] and then we also have epigenome-wide association data using the EPIC array, [phonetic sp] We have some data one whole exome sequencing that was a collaboration with another institute here, and we also have some additional data But the psychological data is something that I was very interested in because I’ve looked at lifestyle data, but I knew that there were other things that could be influencing blood pressure, like perceived stress or perceived racism and discrimination, depression, parenting stress So, I wanted to look at all of those things and what those interaction effects were on African American mothers and their young children And the children are ages three to five And just another thing, if you want to learn more about our study, this is our website, and there are more than — I’m not doing this study alone I have a co-P.I., I have co-investigators, post-docs, and a wonderful research team So, we really do a lot of work collaboratively So, if you want to learn more about our methods, we have published two methods papers on the advanced statistical analysis and we also published on recruitment and psychological measures that we are using in the study We have published on X chromosome analysis We have even — I’ve learned from “Reviewer Two,” so I’ve looked at larger epidemiological samples I’ve worked with Jackson Heart Study and said, “Can I look at your study and, you know, use our conceptual model and run these analyses?” [laughs] So, we looked at effects of genetic risk and perceived discrimination on blood pressure among African Americans in the Jackson Heart Study We have published our data on perceived racial discrimination in DNA and found that it influences DNA methylation in our sample in the InterGEN study And we also recently found that parenting stress was significant — has significantly — was significantly associated with changes in DNA methylation in African American women in this study And this was published in Journal of Clinical and Translational Science So, this study is ongoing, but I just want to talk to you really quickly about this one small study I mention this because if there are any students of post-docs or any junior faculty in the room, I was able to obtain private donor funding by just being in the elevator I was in the elevator talking to a student about the InterGEN study and we were talking about DNA methylation and the different between DNA methylation and the genome and the epigenome, and someone tapped me on my shoulder And she said, “Oh, do you do work in epigenetics?” And I said, “Well, sure.” And she said, “Well can I come to your — if you have a minute, can I come to your office and talk to you about it?” And I said, “Okay.” [laughs] You know, just like, “That’s fine.” And so, she was an alum of Yale University, and she was interested in adverse childhood experiences in DNA methylation And I said, “Well, you know, that’s something we could easily add to our study We could add it to our protocol

and, you know, we could just hire someone to — another person to collect this additional data.” And she said, “Well, how much do you think that will cost?” And I did a quick calculation, and she said, “Okay, I can give you the money for that.” [laughter] So, have your elevator speech ready, is the point of that [laughs] So, what’s near and dear to my heart right now, and what Dr. Grady mentioned in my introduction, is the Flint water crisis, and why I want to look at genomics of lead exposure and why this would be something important to me Remember I talked about Dr. Candace Covington She was my master’s advisor And at the time, where I went to school, we had to do a master’s thesis You didn’t have to publish it, but working with Dr. Covington, you absolutely had to publish this work So, as I mentioned, I had a mobile clinic And I saw a lot of children that were coming to my mobile clinic and they would have signs and symptoms of lead poisoning I would test their lead levels and they would be below five micrograms per deciliter, which is the CDC guidelines for treatment: it has to be over five micrograms per deciliter And I thought, “What’s going on with these kids? Why do they have these signs and symptoms, but they don’t have high lead levels?” So, my master’s thesis, I looked at allelic variation in environmental lead exposure and found that 46 percent of these kids tested heterozygous for the RSA [phonetic sp] gene If you are heterozygous for the RSA gene, you have — it can cause demyelination [phonetic sp] of the neurons, and you can have greater uptake of lead, even at small amounts, which leads to the signs and symptoms that you see of kids that are lead poisoned For kids that are heterozygous for the RSA gene, they typically end up with a condition called metachromatic leukodystrophy, which results in regression of developmental milestones, and they die in early infancy But with the heterozygous variation, you really wouldn’t notice this unless you were genetically tested for it And, after some digging and the work done by Dr. Peretz, I even found that people with African ancestry have an even greater risk of being heterozygous for the RSA gene, which results in this condition called arylsulfatase A pseudodeficiency So, you can imagine how I felt when I heard the news of the Flint water crisis I’m originally from Michigan I come from a town that’s similar in demographics as Flint And I just could not believe that the governor of Michigan would change the water source of Flint, Michigan from Detroit water source to the Flint River, a contaminated river that everyone knows that’s contaminated, in an attempt to save $100 a day So, more than 18 months went by before the water crisis was unveiled, and residents were eating, drinking, bathing, and consuming contaminated water And here, four years later, people are still consuming water that may still not be very safe So, I was very upset about it, to say the least, and I wrote it down Because that was one of the things that my mentors really instilled in me Like, if you think this is a problem, write it down [laughs] And I sent this commentary to NPH Genomic Medicine and I talked about how these CDC guidelines may not be accurate, particularly for people that are of African ancestry and that may have this arylsulfatase A pseudodeficiency, and what can we do, as health providers, to address this risk? And then, I talked about, “This is what symptom science is all about.” You see these symptoms, we know something is going on, this is what NINR is talking about when we talk about symptom science So, I talked about what I think should happen I think people should be tested not only, you know, children, but everyone in Flint How do you treat this? You treat it just like you would treat lead poisoning You give them iron supplements, green, leafy vegetables, high-calcium diet So, it’s not a very expensive intervention but it can mean the world to staving off the long-term effects So, this is a project that I’m working on and I plan to submit this proposal to NINR [laughs] No pressure And, as Dr. Grady mentioned, I was fortunate enough to be nominated by NINR and selected by President Obama to receive the Presidential Early Career Award

for Scientists and Engineers, and I’m the fourth nurse to receive it We have another awardee right here in the room, Dr. Jessica Gill And with that comes additional funds to expand the work that you’re currently doing So, I’m using the knowledge that I gained at MIT to expand the work that I’ve done in genomics to use whole-genome sequencing as a screening tool in the community for cardiovascular outcomes I even wrote a paper about it, [laughs] on what I think the roles of nurses and nurse scientists should be in whole-genome sequencing Because I think that, in a lot of ways, that nurses are very under-utilized in terms of what we can do, and our knowledge base, and what we can contribute to these types of studies And we are very well-positioned to lead these studies and to do the work, not only with the recruitment and the retention, but do the laboratory work, the computation, and so on Why do I think this is important? I use this as an exemplar of familial hypercholesterolemia This is a condition that is commonly tested for in whole-genome sequencing studies, but a lot of times, minority populations are not included in these studies And we know that African Americans suffer from familial hypercholesterolemia and we don’t usually find this out until they have sudden cardiac death But this is something that can be easily treated with statins, and people can continue to live if we know that there is a genetic risk for familial hypercholesterolemia So, paying it forward: that’s what I plan to do now I have benefitted from great mentorship and from, you know, generous funding And so, I just want to take a minute and talk about a couple of my recent mentees This is Dr. Michelle Wright She is currently at — she was a post-doc on my InterGEN study that is funded by NINR She and I have published more than 10 papers together, and she is currently faculty at Emory University and is moving on to a tenured track position at U.T. Austin this fall And then, there’s Dr. Veronica Barcelona de Mendoza, who was also a post-doc on the InterGEN study She’s currently Assistant Professor at the Yale School of Nursing She has been successful in receiving a K01 [phonetic sp] from NINR, of which I am her primary mentor She has received the Loan Repayment Program grant from National Institute of Minority Health and she has been a Jonas Policy Scholar with the American Academy of Nursing, and she is also a participant in the PRIDE program that I participated in many years ago at Washington University in St. Louis, to learn more about advanced statistical analyses and genomics And then, last summer, I actually held a summer intensive where I wanted to have diverse scholars from across the country come to Yale, so we could talk about mentorship and career development and things that would be helpful for them in their careers, whatever they planned to do And this is a picture of some of our scholars And as you can see here, we have Dr. Paule Joseph from NINR that participated, Dr Veronica Barcelona de Mendoza, and many other scholars I also include Dori Dumas here, who is a very good friend of mine, but other than that, I have her here because I brought in a lot of community leaders to talk to these scholars, to discuss how they can go through community organizations to help them recruit in their studies And she is the president of the local chapter of the NAACP in New Haven, Connecticut And while I was in this summer intensive, I was very motivated by this group of scholars, in particularly Paule is one of them, and Veronica is another one And I wanted to talk about how we can improve omics-based research and precision health in minority populations What can we do, as nursing scientists, to get more people involved in research, and how we can better mentor junior faculty to continue in this work So, in addition to writing this paper, as soon as I got to NYU, we submitted a Center Grant on this topic Because if I write a paper about it, I think I should probably participate in what I — [laughs] the recommendations that I’m making for people to improve in that area So, we wrote An Exploratory Center on Precision Health Among Diverse Populations We received a very — a pretty good score, and we are waiting to hear the outcome of this

But this will support research of junior faculty, just like I was supported with the P20 pilot when I first started my career And like I said, it meant the world to me and really jumpstarted my career I’ve also applied as a co-P.I. and then, with the P20, I’m co-P.I., and many other excellent faculty at New York University And this particular R25 is looking at research education in cardiovascular disorders And we’re looking at targeting this toward baccalaureate and master’s level students and, in particular, minority students So, as you can see, I’m trying to get undergraduate, graduate, and junior faculty in the pipeline to continue the work that I was fortunate enough to have excellent mentorship to do So, I’m going to end here I want to just thank you for your time and attention Of course, I definitely want to thank our funders, NINR, RWJ, [phonetic sp] all the other funders, our research team, mentors and collaborators And this is my family This is what they do while I’m writing all these grants and writing papers They’re out at the baseball game And this is David Housman, my mentor at MIT. [laughs] He’s out at the football game with my son and my husband and my daughter, she’s at a quinceanera having a good time [laughter] So, again, thank you so much, and I’m happy to take any questions Please feel free to come to either one of the mics here if you have any questions for me [applause] [music playing]