Dates of Funding: 2022-2024
I am a Post-doctoral Fellow in the Department of Pediatrics, Section of Nutrition at the University of Colorado – Anschutz Medical Center, supported by the Ruth L. Kirschstein National Research Service Award T32 Research Fellowship in Nutrition at the University of Colorado – Anschutz Medical Campus (CU – Anschutz). My research interest is in understanding the interactions of nutrition, maternal intrauterine exposures, and epigenetics on obesity risk in childhood. My long-term career goal is to establish myself as an independent physician scientist critically assessing the most optimal nutritional strategies for children at high risk of obesity and associated co-morbidities in the context of their interaction with genetic predisposition, susceptibility conferred via intrauterine exposures, and their effects on infant and child growth. My interests lie in understanding the how the totality of these exposures and potential predictors can be moderated by evidence based nutritional interventions established earlier and sustained throughout the life course.
Differences in childhood obesity risk may appear in infancy, suggesting that factors driving obesity begin operating very early in life. Neural, metabolic, and hormonal networks regulating energy balance are established in utero and are likely influenced by maternal exposures, including nutrition. Human studies have shown that such networks may be determined by epigenetic modifications, of which DNA methylation is the most well studied to date. Studies also indicate that maternal one carbon (1C) nutrient intake, such as that of folate and choline, peri-conceptionally and during pregnancy can influence both offspring adiposity and DNA methylation. Few studies, however, have aimed to evaluate the mediation of adiposity risk by DNA methylation in relation to its association with maternal 1C nutrient concentrations. Differential DNA methylation, influenced by maternal 1C nutrient status, may serve as a marker at birth that predicts risk of adiposity, informing the need for additional clinical monitoring or alternative nutritional recommendations to prevent exacerbated growth.
For my NORC pilot award I propose to determine whether intrauterine exposure to maternal concentrations of folate and choline through 27 weeks gestation influences offspring adiposity and is mediated by DNA methylation identified at birth by leveraging data obtained from the Healthy Start Study (R01 DK076648, PI: Dabelea) an ongoing a large, multi-ethnic, prebirth cohort that has collected DNA methylation at birth in ~600 infants and longitudinal adiposity measures at birth, 5 months, and 5 years of age in the offspring. More specifically, in this population of mother-infant dyads in which maternal intake of these two 1-carbon nutrient precursors is outside of recommended intake ranges during pregnancy, I aim to 1) precisely elucidate the effect of excessive folate status and inadequate choline status, based on maternal serum concentrations, on infant and child adiposity outcomes, and 2) examine mediation by DNA methylation in offspring cord blood. Our results will contribute to knowledge and may clarify rising concerns regarding “population wide excess folate status” especially in pregnant women due to dose exposure and the potential for long term adverse effects on offspring health. This investigation will also indicate whether such status has any potential compensatory effect on offspring anthropometric outcomes or DNA methylation in the context of low choline concentrations amongst the population of maternal-infant dyads studied. Additionally, the NORC award will facilitate my career goals of obtaining a future career development grant and establishing independently funded research.
Dates of Funding: 2022-2024
I am a Postdoctoral Fellow in the Department of Pediatrics, Section of Developmental Biology at CU-AMC. My research sits at the complex intersection of nutrition, neuroscience, and developmental biology. During pregnancy and early postnatal life, malnutrition can impair brain development, resulting in irreversible cognitive and psychiatric conditions. There is no question that adequate nutrition is vital for brain growth and maturation, but for many nutrients it remains unclear how deficiency alters neurodevelopmental programming at the cellular and molecular level. My NORC pilot project uses a zebrafish model to investigate the cellular consequences of omega-3 polyunsaturated fatty acid (omega-3 PUFA) deficiency during brain development. Omega-3 PUFA-deficient animals exhibit impaired immune responses by microglia, the brain’s resident macrophages. Microglia also regulate the formation and elimination of myelin, which insulates axons and increases the speed of nerve impulses. However, it is not known whether omega-3 PUFA deficiency culminates in the aberrant regulation of myelination. I will test this hypothesis by assessing whether omega-3 PUFA deficiency alters the microglial transcriptome (Aim 1), myelin maturation and morphology (Aim 2), and the dynamic microglia-myelin interactions in vivo (Aim 3). This work could provide insight into nutritional strategies for optimizing infant health and preventing neurodevelopmental disorders.
Dates of Funding: 2022-2024
I am currently a Post-Doctoral Fellow at the University of Colorado, Anschutz Medical Campus in the Division of Renal Disease and Hypertension. My long-term career goal is to become an independent research scientist with a focus on the interaction of lifestyle behaviors and health outcomes in individuals with kidney disease. I am supported by an NIDDK F32 fellowship, which focuses on patients with autosomal dominant polycystic kidney disease (ADPKD). ADPKD is the most commonly inherited progressive kidney disease. Overweight and obese phenotypes have been associated with disease progression in early-stage ADPKD. Daily caloric restriction (DCR, 34% restriction per day from baseline weight maintenance requirements) may aid in weight loss and ultimately slow ADPKD disease progression. Weight loss via DCR may cause alterations in kidney oxidative metabolism and insulin sensitivity that can affect ADPKD disease progression. For my NORC pilot award, I will assess kidney oxidative metabolism and insulin sensitivity by leveraging an ongoing R01-funded trial (NCT04907799) in DCR vs. control groups at baseline (BSL) and 2 years. I will also utilize the clinical outcome measures performed in the parent trial to address the subsequent novel aims: Aim 1: Compare kidney oxidative metabolism and insulin sensitivity at BSL and 2 years in adults with ADPKD. Aim 2: Define the relations among changes in kidney oxidative metabolism, insulin sensitivity, total kidney volume, and weight over 2 years. Currently, it is unknown if weight loss via DCR modifies renal energy expenditure and substrate utilization. Collectively, this award will provide an opportunity to collect novel preliminary data and training for a future career development grant.
Dates of funding: 2021-2023
I am currently a Research Instructor at the University of Colorado, Anschutz Medical Campus in the Department of Pediatrics, Nutrition Section. My long-term goal is to become an independent, NIH-funded investigator with a basic science research program focused on the role of thyroid hormones and their metabolites in regulating metabolism. Currently, I hold a KL2 Mentored Career Development Award through the Colorado Clinical and Translational Sciences Institute (CCTSI), where I am investigating the role of 3,3`-T2, a thyroid hormone metabolite, in the cardiac recovery after myocardial infarction. I am also a recipient of L’Oréal USA’s 2020 For Women in Science (FWIS) Fellowship. My FWIS proposal assesses whether 3,3'-T2, in animal models with late-stage type 2 diabetes, induces proliferation of β-cell. Thus, my NORC pilot project supports my overall career goals as it seeks to deeply investigate the role of thyroid hormones and their metabolites’ on β-cell function. With this NORC pilot award, I aim to generate enough preliminary data to apply for NIH-R-level funding.
Dates of funding: 2021-2023
Pediatric nonalcoholic fatty liver disease (NAFLD) is an increasingly prevalent obesity-related co-morbidity in youth. While experimental studies support associations of excess added sugar (AS) and sugary beverage (SB) intakes with NAFLD, findings from observational studies have been inconsistent, in-part due to measurement error associated with self-reported dietary assessment methods. The blood carbon isotope ratio (CIR) has shown promise as an objective biomarker of AS intake in the U.S., and may be a solution to limit this error, but few studies have tested it in pediatric populations. This proposal will address this gap by measuring serum CIR in three prospective pediatric studies (one controlled feeding intervention and two longitudinal cohort studies) and examining correlations with self-reported AS and SB intake in each study (Aim 1). We will also assess whether regression calibration of self-reported AS and SB intakes with serum CIR alters associations with hepatic fat (Aim 2) and whether the PNPLA3 rs738409 risk allele, a strong genetic risk factor for NAFLD, modifies sugar-hepatic fat associations (Aim 3). This proposal will establish feasibility in using serum CIR as a biomarker of AS and SB intake in youth and facilitate the applicant’s career goal of establishing an independently funded research program.
Dates of funding: 2021-2023
Loss of ovarian function greatly increases the risk of non-alcoholic fatty liver (NAFLD) in humans and rodents, and therapies available to treat this disorder are limited. In addition to other mechanisms that have been described, it’s likely that changes in adipose tissue in the postmenopausal state also contribute to NAFLD. Specifically, menopause and ovariectomy (OVX) favor the accumulation of pro-inflammatory bone marrow-derived adipocytes (BMDA) that may change the cellular composition of abdominal fat by enriching it with adipocytes that export harmful factors to the liver, and mechanisms that modulate BMDA infiltration are poorly understood. I hypothesize that limited calorie diets can restrict abdominal BMDA infiltration to improve NAFLD in rodents that undergo OVX, and I also propose that BMDA play a substantial direct role in mediating OVX-induced NAFLD development. To test this, 1) I will use weight maintenance and caloric restriction diets in mice that undergo OVX to determine if this strategy reduces BMDA infiltration and limits NAFLD progression, and 2) I will use genetic ablation of BMDA in OVX mice to test their direct contribution to NAFLD. Data obtained from these aims will provide novel insight into OVX-induced NAFLD and provide new therapeutic targets to treat this disorder.
Dates of funding: 2021-2023
My clinical and research interests are in fetal and neonatal growth and nutrition. Intrauterine growth restriction (IUGR) is a common complication of pregnancy. Individuals with IUGR are not only at increased risk for morbidity and mortality in the perinatal period but are also at increased risk of developing metabolic diseases, such as type 2 diabetes, in adulthood. My long term research goals are to understand the factors, such as hormones and nutrients, that regulate fetal growth and to understand how the fetus adapts to abnormal nutrient availability. This knowledge is essential in order to develop strategies to mitigate abnormal fetal growth patterns and improve lifelong metabolic health. My NORC pilot project aims to understand how insulin-like growth factor 1 (IGF-1) and insulin, which are two critical fetal growth hormones that are known to be low in the IUGR fetus, work together to coordinate fetal nutrient availability to support fetal growth and protein accretion.
Dates of funding: 2021-2023
I am a Senior Instructor in the Division of Endocrinology, Metabolism, and Diabetes and the Director of the NORC Lipidomics Core Laboratory at CU-AMC. The overall objective of my research is to expand our knowledge of lipid-induced insulin resistance and reveal potential novel lipid targets to modify muscle insulin sensitivity. My NORC pilot project focuses on the role of oxidized lipids in insulin resistance. The first goal of this proposal is to explore the role of oxidized lipids in the accumulation of sarcolemmal ceramides and insulin resistance in skeletal muscle. The second goal is to quantify oxidized lipid levels in plasma of endurance trained athletes, sedentary lean controls, and individuals with obesity and/or T2D by liquid chromatography-tandem mass spectrometry (LC-MS/MS). We anticipate that these outcomes will provide clinical significance by identifying signaling pathways and mechanisms of accumulation of localized ceramides which can ultimately be targeted for the prevention and treatment of T2D.
Dates of funding: 2020-2022
My long-term research interests are focused on understanding the molecular adaptations governing pathological myocardial remodeling, exercise intolerance, and the progression to heart failure in patients with congenital heart disease. The lab utilizes several unique tools to address the mechanisms of cardiac dysfunction including whole animal and cell culture-based models, as well as access to a meticulously preserved Pediatric Tissue and Blood Bank here at the University of Colorado Anschutz Medical Campus. My research objective is to improve our molecular understanding of heart failure in the pediatric congenital heart disease population with the goal of identifying efficacious therapies through basic science and clinical investigations and improving outcomes in this vulnerable group . I plan to accomplish these goals through several avenues including: 1) better understanding the molecular adaptations of pediatric heart failure, 2) identification of novel therapeutic targets, 3) animal and cell-based model development, 4) diagnostic and prognostic biomarker assessment, and 5) multi-omics data integration. My ultimate career goal is to be an independently funded full-time professor with expertise in pediatric cardiovascular disease, who runs a lab that contributes to the treatment and prevention of heart failure, and who participates in the training and mentoring of a diverse set of budding researchers.
My long-term research career goals include studying novel approaches to personalize obesity treatment using a combination of tools (e.g. nutrition interventions, pharmacotherapy, bariatric surgery) to achieve optimal weight-related health outcomes, and to minimize disparities driven by the social determinants of health and stigma.
Following an Internal Medicine/Pediatrics residency, I completed a one-year fellowship in pediatric clinical nutrition at the University of Colorado, which provided a broad training experience across the growth and development spectrum (from severe malnutrition to micronutrient deficiency evaluation to acute management of severe obesity comorbidities). I was then was accepted into the University of Colorado’s 3-year NIH T32 Nutrition fellowship (PI: Krebs). After a year working with Dr. Janet Snell-Bergeon in nutritional epidemiology, in August 2017, I transitioned to working with Drs. Richard Boles, Thomas Inge, and Megan Kelsey in the Bariatric Surgery Center at Children’s Hospital Colorado. This transition allowed me to pursue research questions within the patient population that I am most passionate about: adolescents and young adults with severe obesity. This work has included receiving an Investigational New Drug application through the FDA and a 2019-2020 Nutrition Obesity Research Center (NORC) pilot & feasibility award to study anti-obesity medications (phentermine and topiramate) among adolescents and young adults who do not achieve adequate risk reduction after bariatric surgery. My ongoing desire to effectively address health disparities, has also led me to pursue a Master in Public Health (MPH) during fellowship. This MPH program has complemented my fellowship training with experiential learning in areas of health behavior theory, health care equity, qualitative methods, and program planning/implementation/evaluation.
I am interested in conducting clinical trials that evaluate the effects of adjunctive treatments (to lifestyle-based and surgical interventions) for adolescents and young adults with severe obesity, and in particular, the use of anti-obesity pharmacotherapy. Testable questions that are unanswered in the field of anti-obesity pharmacotherapy among adolescents include: Can anti-obesity medications additively or synergistically augment the effects of bariatric surgery? When in the perioperative timeline is it most effective to use pharmacotherapy? Which medications are best for improving specific obesity co-morbidities before and after surgery? What individual patient and psychosocial characteristics predict a positive response to one agent (or combination) over another? And, how should “success” of anti-obesity medications be defined in pediatrics? To advance my understanding of anti-obesity pharmacotherapy, I attended the Advanced Therapies for Pediatric Obesity Workshop presented by the University of Minnesota Masonic Children’s Hospital Pediatric Weight Management Program in October 2017. And I am currently completing a pharmacogenomics certificate program, to better understand how we may be able to personalize anti-obesity medication regimens. I have created standardized clinical protocols for use of anti-obesity pharmacotherapy for the entire Lifestyle Medicine Program (including the Bariatric Surgery Center). And I am the clinical lead for initiating and monitoring anti-obesity pharmacotherapy before and after bariatric surgery. I recently transitioned to faculty as an Assistant Professor in the Department of Pediatrics, Section of Nutrition and was hired as the second medical provider within the Bariatric Surgery Center at Children’s Hospital Colorado.
Transgender (trans) people have a gender identity and/or gender expression that does not align with their sex assigned at birth (SAB). Many trans people experience associated distress known as gender dysphoria. Health care disparities among trans people are prevalent, related to gender dysphoria, fears of discrimination, access to medical/surgical care and other barriers. Among the many health care disparities faced by trans people, studies have reported on decreased physical activity and healthy eating habits as well as increased tobacco smoking, alcohol use and drug use. My quality improvement project during endocrine fellowship revealed higher rates of obesity among both trans women and trans men compared to the general adult population of Colorado. Research locally and around the world tries to better understand the basis for and evaluate solutions to reduce differential health outcomes based on gender identity.
As an early career endocrinologist at the University of Colorado School of Medicine (CUSOM), my academic trajectory is to explore the impacts of obesity, aging and gender-affirming hormone therapy (GAHT, or using sex hormones of the affirmed gender) on cardiometabolic risk in trans people. My current research compares vascular endothelial function and aging in trans women and men on chronic GAHT with the same parameters in cisgender (cis) women and men, individuals whose gender identity aligns with their SAB. These data will provide preliminary data for further investigations on the effects of sex steroids in trans and cis people. My interest in trans research has a foundation in years of volunteer work within the trans and other sexual/gender minority communities. Over the years, I have also heard from trans patients about continued stigma within medicine regarding access to culturally sensitive and comprehensive care. Trans patients deserve evidence-based best practices for health care delivery, particularly in the setting of GAHT, which has been associated with weight gain and an increased risk cardiovascular disease (CVD) and venous thromboembolism in trans women and possibly trans men. Whether gonadectomy (after GAHT, based on clinical practice guidelines) affects CVD risk is yet to be determined.
In September 2017, I co-founded the UCHealth Integrated Transgender Program (ITP) with my mentor, Dr. Micol Rothman, and other specialists in psychiatry, internal medicine, gynecology and plastics and reconstructive surgery, to provide safe and comprehensive care to our trans patients during a single clinic visit within the Endocrinology Clinic. ITP also educates providers, staff and learners across the hospital system and within the community. We received a 2018 University of Colorado President’s Diversity & Inclusive Excellence Grant, the 2019 University of Colorado Hospital Medical Staff Award for Excellence in Clinical Innovation and a 2019 One Colorado Ally Award. We are collecting qualitative (e.g., patient and provider needs assessments) and quantitative (e.g., Pap test and other cancer screening compliance, hormone monitoring, body mass index [BMI] and body composition changes, laboratory trends, pre-/post-Provider Education Day knowledge differences) data. We are establishing a Community Advisory Board to engage stakeholders in developing ideas for future research collaborations and participant recruitment. I am also spearheading the creation of a registry of trans patients at UCHealth and will collect prospective data on health outcomes. Working with the Division of Plastic and Reconstructive Surgery, a new plastic surgeon will join the ITP team in Sept 2019, increasing access to gender-affirming surgery to our patients.
To learn more about trans health research, I met Dr. Guy T’Sjoen (Ghent University Hospital, Belgium) and Dr. Martin den Heijer (Amsterdam University Medical Center, the Netherlands) as part of a 2017 American Association of Clinical Endocrinologists/American College of Endocrinology (AACE/ACE) Dr. Lewis E. Braverman Educational Fund Travel Grant. Both are endocrinologists and primary investigators of the European Network for the Investigation of Gender Incongruence (ENIGI), the first collaboration to create a multicenter, multinational, standardized treatment and follow up protocol to prospectively investigate the effects of GAHT in trans people. Since then, we have collaborated on a workshop about GAHT outcomes at the European Professional Association for Transgender Health (EPATH) in April 2019 and wrote a narrative review on feminizing GAHT. I have also submitted a proposal to conduct subgroup analyses on existing ENIGI data to see if/how BMI and age influence various health outcomes in that cohort of patients. I am serving on the U.S. Professional Association for Transgender Health (USPATH) 2019 Conference Scientific Review and Awards Committees, while also part of a symposium on screening tests in trans people.
I have ongoing support of my mentorship committee and the CUSOM Department of Medicine, Division of Endocrinology, Metabolism & Diabetes to help achieve their vision of cultivating interdisciplinary trans research. Though early in my career, I have already established myself as a physician advocate dedicated to improving health care/outcomes for trans patients through interdisciplinary clinical translational research and international collaboration, with a focus on obesity and aging.