Rachel Mintz
Program: Biomedical Engineering
Current advisor: Gwendalyn J Randolph, PhD
Undergraduate university: Columbia University
Research summary
The omentum, a visceral fat pad along the stomach’s greater curvature, plays a pivotal role in steady-state immunity, inflammation, and cancer. Using fate mapping, omental photoconversion, and bone marrow transplants, we show that peritoneal macrophages interact with the omentum, shaping their differentiation and maturation. As an immune hub, the omentum drives peritoneal inflammation by serving as a reservoir for immune cells, producing pro-inflammatory cytokines, and modulating metabolism. In ovarian cancer, it is the earliest and most dominant metastatic site, though the mechanisms guiding tumor tropism remain unclear.
This research redefines the omentum’s role in immunity, metastasis, and cachexia. We show that the omentum contributes to peritoneal macrophage differentiation at steady state, reinforcing its role in immune regulation. Contrary to the prevailing view that adipocytes drive ovarian cancer metastasis to the omentum, we identify TNF signaling, independent of the omentum, as a key driver of tumor burden and establish that adipocytes were dispensable. Additionally, we demonstrate that chemotherapy-induced cachexia is a severe inflammatory condition that depletes omental adipose tissue in the absence of tumor burden. Together, these findings reveal the omentum as a dynamic immune and metabolic interface at the nexus of homeostasis, inflammation, and disease progression.
Graduate publications
Han J, Gallerand A, Erlich EC, Helmink BA, Mair I, Li X, Eckhouse SR, Dimou FM, Shakhsheer BA, Phelps HM, Chan MM, Mintz RL, Lee DD, Schilling JD, Finlay CM, Allen JE, Jakubzick CV, Else KJ, Onufer EJ, Zhang N, Randolph GJ. 2024 Human serous cavity macrophages and dendritic cells possess counterparts in the mouse with a distinct distribution between species. Nat Immunol, 25(1):155-65.
Canales-Herrerias P, Uzzan M, Seki A, Czepielewski RS, Verstockt B, Livanos AE, Raso F, Dunn A, Dai D, Wang A, Al-Taie Z, Martin J, Laurent T, Ko HM, Tokuyama M, Tankelevich M, Meringer H, Cossarini F, Jha D, Krek A, Paulsen JD, Taylor MD, Nakadar MZ, Wong J, Erlich EC, Mintz RL, Onufer EJ, Helmink BA, Sharma K, Rosenstein A, Ganjian D, Chung G, Dawson T, Juarez J, Yajnik V, Cerutti A, Faith JJ, Suarez-Farinas M, Argmann C, Petralia F, Randolph GJ, Polydorides AD, Reboldi A, Colombel JF, Mehandru S. 2024 Gut-associated lymphoid tissue attrition associates with response to anti-α4β7 therapy in ulcerative colitis. Sci Immunol, 9(94):eadg7549.
Lam SF, Bishop KW, Mintz R, Fang L, Achilefu S. 2021 Calcium carbonate nanoparticles stimulate cancer cell reprogramming to suppress tumor growth and invasion in an organ-on-a-chip system. Sci Rep, 11(1):9246.
Fan J, Cheney PP, Bloch S, Xu B, Liang K, Odonkor CA, Edwards WB, Basak S, Mintz R, Biswas P, Achilefu S. 2021 Multifunctional Thio-Stabilized Gold Nanoparticles for Near-Infrared Fluorescence Detection and Imaging of Activated Caspase-3. Curr Anal Chem, 17(8):1182-1193.