Jonathan R. Brestoff, MD, PhD, MPH

Jonathan R. Brestoff, MD, PhD, MPH

Associate Professor (tenured), Pathology and Immunology
Director, Immunometabolism Initiative

Division

  • Laboratory & Genomic Medicine

Education

  • BS: Skidmore College (2008)
  • MPH: University College Cork – National University of Ireland, Cork (2010)
  • MD/PhD: Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, (2016)
  • Residency: Clinical Pathology, Barnes-Jewish Hospital/SLCH/Washington University School of Medicine (2019)

Related Links

Board Certification

  • American Board of Pathology, Clinical Pathology

Recognition

  • Barry M. Goldwater Scholarship
  • George J. Mitchell Scholarship
  • Joseph C. Palamountain Award for Young Alumni Achievement, Skidmore College
  • Roy G. Williams Award, University of Pennsylvania
  • Endocrine Society Award for Medical Student Achievement
  • Paul E. Strandjord Young Investigator Award, ACLPS
  • William L. Roberts Award with Distinction, ACLPS
  • Children’s Discovery Institute Fellowship
  • Career Award for Medical Scientists, Burroughs Welcome Fund
  • NIH Director’s Early Independence Award (DP5)
  • AAI Early Career Faculty Award
  • American Society for Clinical Investigation (ASCI) Young Physician-Scientist Award
  • Cell Metabolism Best of 2021 special issue
  • Cell Metabolism Best of 2022 special issue

Clinical Interests

  • Immunology diagnostic testing
  • Implementation of spectral flow cytometry for clinical use

Research Interests

The immune system is able to control the metabolism of many organ systems, and disruption of these immunometabolic pathways contributes to the development of metabolic diseases such as obesity and type 2 diabetes. The Brestoff Lab’s research focuses on understanding how immune cells regulate the function of white, beige, and brown fat to maintain normal metabolism and support adaptation to physiologic challenges such as high-fat diet feeding, changes in environmental temperature, and fasting. We have a special interest in understanding a process called intercellular mitochondria transfer, its molecular mechanisms, and how it contributes to the maintaining the function of organ systems in health and disease (Cell Metabolism 2021, 2022a, 2022b; Nature 2023). We employ cutting-edge techniques in immunology, metabolism, and mitochondria biology to study the immunometabolic pathways that are required for metabolic health and that contribute to disease pathogenesis. Ultimately, our goal is to discover novel biological pathways that can be targeted therapeutically or that can be leveraged to develop new diagnostic tests. We have developed multiple technologies with real-world applications, including mitochondria transplantation for inherited mitochondrial diseases (Nature Metabolism, 2024) which is progressing into clinical trials, an immunology-focused diagnostic test that is currently in clinical use, a metabolic cage analytic tool called Clambake that was successfully licensed to a major industrial partner, and a novel anti-obesity drug that we are developing.

Selected Publications

PubMed Search
Nakai R (co-first), Varnum S (co-first), Field RL, Shi H, Giwa R, Jia W, Krysa S, Borcherding N, Saneto R, Tsai R, Suganuma M, Ohta H, Yokota T, Brestoff JR. Mitochondria transfer reduces the morbidity and mortality of Leigh Syndrome. Nature Metabolism, 6 (10): 1886-1896, 2024.
Jia W, Giwa R, Moley JR, Smith GI, Petersen MC, Field RL, Abousaway O, Kim AS, Coffey SR, Varnum S, Wright JM, Zhang X, Krysa S, Lodhi IJ, Abumrad NA, Klien S, Diamond MS, *Brestoff JR. MXRA8 promotes adipose tissue whitening to drive obesity. bioRxiv 2024.01.31.578211.
Borcherding N and Brestoff JR. The power and potential of mitochondria transfer. Nature 623 (7986): 283-291, 2023.
Yang Y, Yuan J, Field RL, Ye D, Hu Z, Zu K, Xu L, Gong Y, Yue Y, Kravitz A, Bruchas MR, Cui J, Brestoff JR, Chen H. Torpor-like hypothermic and hypometabolic state induced by ultrasound. Nature Metabolism 5: 789-803, 2023
Kim DH, Wang Y, Jung H, Field RL, Zhang X, Liu TC, Ma C, Fraser JS, Brestoff JR, Van Dyken SJ. A type 2 immune circuit in the stomach controls mammalian adaptation to dietary chitin. Science381(6662): 1092-1098, 2023.
Borcherding N (co-first), Jia W (co-first), Giwa R, Field RL, Moley JR, Kopecky BJ, Chan M, Yang BQ, Sabio JM, Walker E, Osorio O, Bredemeyer A, Pietka T, Alexander-Brett J, Moley CS, Artyomov MN, Abumrad NA, Schilling JD, Lavine K, Crew C, Brestoff JR. Dietary lipids inhibit mitochondria transfer to macrophages to divert adipocyte-derived mitochondria into blood. Cell Metabolism, 34(10): 1499-1513.e8, 2022.
Brestoff JR, Wilen CB, Moley JR, Li Y, Zou W, Malvin NP, Rowen MN, Saunders BT, Ma H, Mack MR, Hykes BL, Balce DR, Orvedahl A, Williams JW, Rohatgi N, Wang X, McAllaster MR, Handley SA, Kim BS, Doench JG, Zinselmeyer BH, Diamond MS, Virgin HW, Gelman AE, Teitelbaum SL. Intercellular mitochondria transfer to macrophages regulates white adipose tissue homeostasis and is impaired in obesity.  Cell Metabolism33 (2): 270-282.e8, 2021.
Brestoff JR and Artis D. Immune cell regulation of metabolic homeostasis in health and disease. Cell 2015; 161(1): 146-160.
Brestoff JR, Kim BS, Saenz SA, Stine RR, Monticelli LA, Sonnenberg GF, Thome JJ, Farber DL, Lutfy K, Seale P, Artis D. Group 2 innate lymphoid cells promote beiging of white adipose tissue and limit obesity. Nature 2015; 519: 242-246.
Brestoff JR and Artis D. Commensal bacteria at the interface of host metabolism and the immune system. Nature Immunology 2013; 14(7): 676-684.

Assistant
Dionne Brierton
314-362-3186
bdionne@wustl.edu
BJCIH Room 4410