Description of Research Expertise
The Merrick laboratory is located within the Institute for Diabetes, Obesity and Metabolism (IDOM) at the University of Pennsylvania / Perelman School of Medicine and is affiliated with the Department of Medicine Division of Endocrinology as well as the Cell Biology, Physiology and Metabolism Program.
Obesity and the metabolic syndrome represent a profound public health challenge for which there are few effective therapeutics. Fundamentally, obesity arises in the setting of nutrient excess, which stimulates adipose tissue expansion. The healthy growth of adipose tissue depends on the capacity of progenitor cells to undergo de novo adipogenesis. However, the cellular hierarchy and mechanisms governing adipocyte progenitor lineage allocation are poorly understood.
Our research program is focused on understanding the cells types, niche locations and intracellular signaling pathways that regulate mesenchymal progenitor cell activity. Using cutting-edge approaches including single-cell RNA transcriptomics, CRISPR-based rapid mouse model generation and in-vivo lineage tracing, we have discovered several novel progenitor cell populations including Interstitial Progenitor Cells (IPCs) and connective-tissue resident macrophages. IPCs are multipotent progenitors, which can give rise to committed preadipocytes and mature adipocytes. Importantly, we found that IPCs and connective tissue macrophages cohabit the Reticular Interstitium (RI), a fibrous tissue that envelops many organs including adipose depots and represents a novel anatomical niche for mesenchymal progenitors.
Mesenchymal progenitors represent a promising therapeutic target for the treatment of obesity and diabetes. Directing the differentiation of progenitor cells away from a deleterious pro-fibrotic phenotype and towards a metabolically beneficial fate could significantly improve outcomes for patients suffering from the consequences of obesity.
Selected Publications
Chen Y, Liu L, Calhoun R, Cheng L, Merrick D, Steger DJ, Seale P: Transcriptional regulation of adipocyte lipolysis by IRF2BP2 bioRixiv : 2024.
Paneru BD, Chini J, McCright SJ, DeMarco N, Miller J, Joannas LD, Henao-Mejia J, Titchenell PM, Merrick DM, Lim HW, Lazar MA, Hill DA: Myeloid-derived miR-6236 potentiates adipocyte insulin signaling and prevents hyperglycemia during obesity Nature Communications : 2024.
Traynor S, Bhattacharya S, Batmanov K, Cheng L, Weller A, Moore N, Flesher C, Merrick D: Developmental regulation of dermal adipose tissue by BCL11b Genes Dev : 2024.
David Merrick: She didn’t start the fire: Mammary duct epithelial cells suppress adipocyte thermogenesis Cell Metabolism 35 (10): 1679-1680,2023.
Jacob K Sterling, Bailey Baumann, Sierra Foshe, Andrew Voigt, Samyuktha Guttha, Ahab Alnemri, Sam J McCright, Mingyao Li, Randy J Zauhar, Sandra R Montezuma, Rebecca J Kapphahn, Venkata R M Chavali, David A Hill, Deborah A Ferrington, Dwight Stambolian, Robert F Mullins, David Merrick, Joshua L Dunaief: Inflammatory adipose activates a nutritional immunity pathway leading to retinal dysfunction Cell Rep 14 (39): 110942,2022.
Stefkovich M, Traynor S, Cheng L, Merrick D, Seale P.: Dpp4+ interstitial progenitor cells contribute to basal and high fat diet-induced adipogenesis Mol Metab 54 (101357): 2021.
Merrick D, Seale P.: Skinny Fat Cells Stimulate Wound Healing Cell Stem Cell 26 : 801-803,2020.
Merrick David, Sakers Alexander, Irgebay Zhazira, Okada Chihiro, Calvert Catherine, Morley Michael P, Percec Ivona, Seale Patrick: Identification of a mesenchymal progenitor cell hierarchy in adipose tissue. Science (New York, N.Y.) 364 (6438): 2019.
Merrick David, Mistry Kavita, Wu Jingshing, Gresko Nikolay, Baggs Julie E, Hogenesch John B, Sun Zhaoxia, Caplan Michael J: Polycystin-1 regulates bone development through an interaction with the transcriptional coactivator TAZ. Human molecular genetics 28 (1): 16-30,2019.
Merrick D, Sakers A, Kim J, Irgebay Z, Seale P.: “Population Dynamics of Adipocyte Progenitors.” Kroc Lecture, (2018 and 2019)University of Pennsylvania, Perelman School of Medicine and Department of Medicine Research Day, University of Pennsylvania, June 2018 : 2018.
Academic Contact Information
Institute for Diabetes, Obesity and Metabolism
Smilow Center for Translational Research, 12th Floor, Room 179
3400 Civic Center Boulevard
Philadelphia,
PA
19104
Phone: 215-746-8520
Patient appointments: 800-789-7366