Functional Genomics and Cell Biology of Macrophages
Macrophages are immune cells that maintain the homeostasis of all tissues by eliminating more than 200 billion damaged or senescent cells every day via phagocytosis. As we age, however, 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 certain autoimmune diseases and a subset of lymphomas. However, the potential of macrophages as engineered cell therapies remains largely untapped.
Our work is driven equally by curiosity about the diverse forms and functions of phagocytosis in nature and a motivation to enable new treatments for people suffering from incurable diseases. Some of the questions we are interested in are:
What mechanisms do macrophages use to discern between healthy and abnormal cells when making all-or-none decisions about target cell destruction?
What are the barriers to effective macrophage-mediated clearance of cancer cells in primary tumors and metastatic sites?
How can we systematically engineer macrophages to robustly eliminate a wide range of disease-causing cells?
Why does macrophage clearance capacity decline with age, and can this be reversed?
To answer these questions, we develop powerful genetic screening approaches to discover molecules that regulate macrophage function and apply 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.
Team
Ariana Sanchez
Postdoctoral Fellow
BA, Chemistry, Seattle University
PhD, Cell and Molecular Biology, Stanford University
email: ariana.sanchez2@ucsf.edu
Alex Morse
Specialist Scientist
BA, Molecular Biology, Pomona College
email: alex.morse@ucsf.edu
Dillon Pang
Specialist Scientist
BS, Biology, UC San Diego
email: dillon.pang@ucsf.edu
Meredith Fenyo
Undergraduate Researcher
BS in progress, Biology, Stanford University
email: meredith.fenyo@ucsf.edu
Madeline McCanne
BMS Rotation Student
BA, Chemistry, Cornell University
Arianna Doss
Faculty Assistant
BS, Public Health, San Francisco State 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.
Selected Publications
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.
Latest News
October 2023
Ariana Sanchez joins the lab as the lab's first postdoctoral fellow. Welcome!
Ariana joins us from Genentech, where she worked for two years as a Scientist developing high-throughput immune-cell/cancer co-culture assays and receptor interactome discovery methods. Prior to that, she completed her PhD in Cell and Molecular Biology at Stanford University, where she established proximity labeling methods in living organisms. Welcome, Ariana!
The lab also receives funding from the Larry L. Hillblom Foundation, Glenn Foundation/AFAR, UCSF Liver Center, and the CRISPR Cures for Cancer Initiative.
September 2023
Dillon Pang joins the lab as a Junior Specialist, and Madeline McCanne starts her rotation in the lab. Welcome!
The lab also bids farewell for now to An and Manu as they head back to their respective campuses for the fall term. Thank you for all your contributions to starting the lab!
Contact
513 Parnassus Ave
Medical Sciences Building, Rm S-1349A
San Francisco, CA 94143