Current Funding Awardees

Nicholas Chavkin Ph.D.
Assistant Professor
Department of Pediatrics

Age-related loss of Y Chromosome on Metabolic Dysfunction
As men age, a portion of blood cells undergo mosaic loss of the Y chromosome (mLOY), which is the most common post-zygotic mutation in people. Men with mLOY have higher rates of mortality and age-related disease progression, but the effects of mLOY on metabolic dysfunction have not been investigated. In this project, we will test the hypothesis that mLOY affects metabolic dysfunction from diet-induced obesity by establishing and evaluating models of mLOY in human primary blood cells and transgenic mice. Understanding the role of mLOY in metabolic dysfunction could determine new hematopoietic-related mechanisms regulating metabolism and provide new insights into the relationship between aging and obesity.

Stephen McCartney, M.D., Ph.D.
Assistant Professor
Department of Obstetrics & Gynecology
Division of Maternal Fetal Medicine

Determining the Role of Glucose Utilization in Immune Cell Function at the Maternal Fetal Interface
Pregnancy complications including fetal growth restriction, preeclampsia, and preterm birth are linked to both placental inflammation and metabolic dysfunction, yet treatment options remain limited due to gaps in understanding the complex interactions between immune and metabolic processes at the maternal-fetal interface. This proposal investigates how glucose metabolism influences immune cell function at the maternal-fetal interface across normal pregnancy. Using single-cell flow cytometry, transcriptomics, and metabolomics assays, we will assess energy pathway utilization and metabolic phenotypes of immune cells during each trimester of pregnancy. Findings from this study will clarify how immune and metabolic networks coordinate during normal pregnancy and may provide insight into novel pathways to develop targeted therapeutics for pregnancy complications.

Jocelyn Cervantes
Ph.D. Candidate
Department of Medicine
Division of Metabolism, Endocrinology and Nutrition

Does Diabetic Dyslipidemia Stimulate the Expansion of Lipid-associated Macrophages in Diabetic Kidney Disease (DKD), and Does this Augment of Diminish DKD Progression?
Emerging evidence suggests that diabetic dyslipidemia, characterized by elevated triglyceride-rich lipoproteins (TRLs), contributes to DKD progression. Although lipid-laden macrophages (macrophages with engulfed lipids) are often found and expanded in DKD, their role is unclear. Recent single-cell RNA-sequencing identifies a lipid-associated macrophage population in the kidney marked by high TREM2 expression, which is suggested to play a protective rather than detrimental role in people with obesity and DKD. The goal of this Stroum Fellowship is to investigate if lipid-associated macrophages are expanded in the kidney in response to diabetic dyslipidemia and if suppression of these via deletion of TREM2 results in augmented tissue injury and DKD progression.

Megan Capozzi, Ph.D.
Research Assistant Professor
Department of Medicine
Division of Metabolism, Endocrinology & Nutrition

Hepatic Glycogen Control of Insulin and Glucagon Action
Hepatic glycogen is an important source of energy, storing glucose in response to insulin and mobilizing glucose in response to glucagon. Yet, glycogen levels are decreased in patients with diabetes and preclinical efforts to manipulate hepatic glycogen show promise for treatment of diabetes. In this project, we will test the hypothesis that the hepatic glycogen level will affect insulin and glucagon levels and/or hepatic post-receptor signaling to control its own repletion in physiology and pharmacology. We will use mouse models of altered hepatic glycogen storage to assess insulin and glucagon levels and hepatic action in response to meal nutrients and incretin agonism. Findings from this study will provide a basis in future studies to understand how to logically manipulate glycogen to recover the altered energy homeostasis that occurs in metabolic disease.

Huu Hien Huynh, Pharm.D., Ph.D.
Acting Instructor
Department of Laboratory Medicine & Pathology

Assessment of Type III Collagen Turnover in Diabetic Kidney Disease
Diabetic kidney disease (DKD) is a common complication of diabetes that can result in injury to kidney tubular epithelial cells and their microenvironment through stimulation of proinflammatory and profibrotic pathways. About 30% of individuals with diabetes experience kidney disease, which is the major cause of kidney failure, leading to a significantly elevated risk of premature death. Late stages of DKD are marked by interstitial fibrosis with type III collagen being the most abundant collagen in the interstitial space. The goal of this project is to characterize the balance between type III collagen deposition and remodeling across the spectrum of disease by accurately measuring three different regions of type III procollagen using liquid chromatography coupled to tandem mass spectrometry. Assessing the balance of type III collagen deposition/degradation during the development of kidney fibrosis may help to identify patients with deteriorating kidney function, which could improve current strategies for diagnosis, prognosis, and therapeutic monitoring

Haiming Kerr, Ph.D.
Acting Instructor
Department of Medicine
Division of Gerontology and Geriatric Medicine

Sex Differences in Ghrelin Receptor-Regulated Insulin Resistance and Sarcopenic Obesity with Aging
The goal of this study is to characterize the sex differences in age-related declines of insulin sensitivity and sarcopenic obesity (SO) and evaluate the extent to which the ghrelin receptor GHSR-1a mediates these changes. This proposed study will contribute to the development of novel treatments for SO that are currently lacking for both sexes and ultimately benefit older adults with high risks for diabetes.  We hypothesize that GHSR-1a deletion mitigates age-related insulin resistance, obesity and muscle dysfunction in female mice, and these changes in female mice are more robust than in male mice.

Devasena Ponnalagu, Ph.D.
Assistant Professor
Department of Pharmacology

Unravel Mechanistic Role of Chloride Intracellular Channel 4 (CLIC4) in Metabolic Disorders
In this proposal, we aim to determine the effect of CLIC4 on energy balance and its role in adipose tissue and liver physiology upon HFD consumption. In Aim 1, metabolic phenotyping would be performed on wt and clic4-/- mice, post eight weeks of HFD and chow diet consumption. In Aim 2, we will determine the effect of CLIC4 on metabolic changes associated with HFD consumption, via regulating adipose tissue and liver mitochondrial physiology. The outcome of aim 2, will unveil the effect of CLIC4 ablation on mitochondrial function, and the metabolic and genetic pathways that are dysregulated in liver and adipose tissues after HFD consumption. With these experiments, we aim to establish preliminary evidence of how the intracellular chloride channel, CLIC4 is involved in metabolic disorders. This will open up new avenues of exploration that will link abnormal chloride channels and metabolic disorders.