Understanding and harnessing macrophage phagocytosis to eliminate disease-causing cells
Macrophages are immune cells that specialize in an ancient process called phagocytosis: the uptake of particulate matter or other cells. Phagocytosis is critical for all animal life, either as a means of feeding or to maintain homeostasis through clearance of disease-causing material. In humans, macrophages are present in all tissues, and destroy more than 200 billion damaged or senescent cells every day via phagocytosis. Nevertheless, as we age, aberrant cells accumulate and give rise to a wide range of diseases including cancer, neurodegeneration, and atherosclerosis. Why macrophages fail to clear unwanted cells in the context of age-related diseases is not known. Despite our incomplete knowledge, therapies have been developed that can be used to treat disease by stimulating macrophages to precisely eliminate specific cell populations from the body. These therapies have transformed treatment outcomes in some diseases, including a subset of lymphomas. However, macrophage-based immunotherapies are critically limited in most cancers by the ability of tumor cells to suppress macrophage phagocytosis via mechanisms that are largely unknown.
Our work is driven equally by curiosity about the diverse forms and functions of phagocytosis in nature and the urgent need to develop new treatments for people suffering from incurable diseases. Some of the questions we are interested in are:
How do macrophages discern between healthy and abnormal cells?
What are the barriers to macrophage-mediated clearance of cancer cells and how can we overcome them therapeutically?
To answer these questions, we combine powerful genetic screening approaches to discover molecules that regulate macrophage function with biochemical, cell biological, and in vivo experiments to understand how these components work at a mechanistic level. We are particularly interested in genes, metabolites, and processes that have not been studied before and which may point us to entirely new avenues for disease intervention.
Roarke Kamber, PhD
Assistant Professor, UCSF
Department of Anatomy
Bakar Aging Research Institute
Postdoc, Stanford University
PhD, Harvard University
BS, Stanford University
There are openings in the lab for scientists from a wide range of backgrounds.
Postdoctoral Fellows: Please send Roarke an email with your CV, a cover letter, and contact information for 3 references.
PhD Students: We are affiliated with the UCSF Biomedical Sciences and Tetrad Graduate Programs. Prospective students are encouraged to apply to these programs. Admitted students who are interested in learning more about the lab or in a rotation should email Roarke.
Undergraduates: Though we are full for summer 2023, please reach out if you are interested in conducting research in the lab beginning fall 2023.
Junior Specialists: Please apply at this link.
Vorselen, D.*, Kamber, R.A.*, Labitigan, R.L.D., van Loon, A.P., Peterman, E., Delgado, M.K., Lin, S., Rasmussen, J.P., Bassik, M.C., Theriot. J.A. Cell surface receptors TREM2, CD14 and integrin αMβ2 drive sinking engulfment in phosphatidylserine-mediated phagocytosis. bioRxiv (2022).
Yu, H.*, Kamber, R.A.*, Denic, V, 2022. The peroxisomal exportomer directly inhibits phosphoactivation of the pexophagy receptor to suppress pexophagy in yeast. eLife, 11, e74531.
Kamber, R.A., Nishiga, Y., Morton, B., Banuelos, A.M., Barkal, A.M., Vences-Catalan, F., Gu, M., Fernandez, D, Seoane, J.A., Yao, D., Liu, K., Lin, S., Spees, K, Curtis, C., Jerby-Arnon, L., Weissman, I.L., Sage, J., Bassik, M.C., 2021. Inter-cellular CRISPR screens reveal regulators of cancer cell phagocytosis. Nature, 597(7877), pp.549-554.
Wainberg, M.*, Kamber, R.A.*, Balsubramani, A.*, Meyers, R.M., Sinnott-Armstrong, N., Hornburg, D., Jiang, L., Chan, J., Jian, R., Gu, M., Shcherbina, A., Dubreuil, M.M., Meuleman, W., Spees, K., Snyder, M.P., Bassik, M.C., Kundaje, A., 2021. A genome-wide atlas of co-essential modules assigns function to uncharacterized genes. Nature Genetics, 53(5), pp.638-649.
Kamber, R.A.*, Shoemaker, C.J.* and Denic, V., 2015. Receptor-bound targets of selective autophagy use a scaffold protein to activate the Atg1 kinase. Molecular Cell, 59(3), pp.372-381.
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