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Understanding and harnessing macrophage-mediated
cell clearance in cancer and aging
Understanding and harnessing macrophage-mediated
cell clearance in cancer and aging
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
Roarke Kamber
Roarke Kamber
Assistant Professor
Assistant Professor
BS, Stanford University
PhD, Harvard University
Postdoc, Stanford University
email: roarke.kamber@ucsf.edu
Jinglin Zhu
Jinglin Zhu
Postdoctoral Fellow
Postdoctoral Fellow
BA, Biology, Shandong University
PhD, Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences
email: jinglin.zhu@ucsf.edu
Sonal Joshi
Sonal Joshi
Postdoctoral Fellow
Postdoctoral Fellow
BSc, MSc, Biotechnology, Institute for Biotechnology and Bioinformatics, Pune University
PhD, Immunology, International Center for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy
email: sonal.joshi@ucsf.edu
Jun Kim
Jun Kim
Postdoctoral Fellow
Postdoctoral Fellow
BA, Biological Sciences, Seoul National University
PhD, Molecular and Cell Biology, UC Berkeley
email: jun.kim@ucsf.edu
Madeline McCanne
Madeline McCanne
PhD Student
PhD Student
BA, Chemistry, Cornell University
email: madeline.mcanne@ucsf.edu
Trishna Patel
Trishna Patel
PhD Student
PhD Student
BA, Molecular and Cellular Biology, UC Berkeley
email: trishna.patel@ucsf.edu
Alex Morse
Alex Morse
Specialist Scientist
Specialist Scientist
BA, Molecular Biology, Pomona College
email: alex.morse@ucsf.edu
Dillon Pang
Dillon Pang
Specialist Scientist
Specialist Scientist
BS, Biology, UC San Diego
email: dillon.pang@ucsf.edu
Arianna Doss
Arianna Doss
Faculty Assistant
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: Please send Roarke an email with your CV and transcripts if you are interested in working in the lab.
Junior Specialists: Please apply at this link.
Selected Publications and Preprints
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.
Liu, S. J., Zou, C., Pak, J., Morse, A., Pang, D., Casey-Clyde, T., Borah, A.A, Wu, D., Seo, K., O’Loughlin, T., Lim, D.A., Ozawa, T., Berger, M., Kamber, R.A., Weiss, W.A., Raleigh, D.R.#, Gilbert, L. A.# (2024). In vivo perturb-seq of cancer and microenvironment cells dissects oncologic drivers and radiotherapy responses in glioblastoma. Genome Biology, 25(1), 256.
Tycko, J., Van, M., Aradhana, DelRosso, N., Yao, D., Xu, X., Ludwig, C., Spees, K., Liu, K., Hess, G.T., Gu, M., Mukund, A.X., Suzuki, P.H., Kamber, R.A., Qi, L.S., Bintu, L.#, Bassik, M.C.#, 2024. Development of compact transcriptional effectors using high-throughput measurements in diverse contexts. Nature Biotechnology, pp.1-14.
Amaya, L., Abe, B., Liu, J., Zhao, F., Zhang, W.L., Chen, R., Li, R., Wang, S., Kamber, R.A., Tsai, M.C., Bassik, M.C., Majeti, R., Chang, H., 2024. Pathways for macrophage uptake of cell-free circular RNAs. Molecular Cell, 84(11).
Ahn, G., Riley, N., Kamber, R.A., Wisnovsky, S., Moncayo von Hase, S., Bassik, M.C., Banik, S.M. and Bertozzi, C.R., 2023. Elucidating the cellular determinants of targeted membrane protein degradation by lysosome-targeting chimeras. Science, 382(6668).
Chen, Y., Craven, G.B., Kamber, R.A., Cuesta, A., Zhersh, S., Moroz, Y.S., Bassik, M.C. and Taunton, J., 2023. Direct mapping of ligandable tyrosines and lysines in cells with chiral sulfonyl fluoride probes. Nature Chemistry, pp.1-10.
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
Fall 2024
The lab is awarded an NIH/NIAID DP2 New Innovator Award and an award from the American Cancer Society and Yosemite!
The lab is awarded an NIH/NIAID DP2 New Innovator Award and an award from the American Cancer Society and Yosemite!
Summer 2024
Jun Kim joins the lab as a postdoctoral fellow and Trishna Patel joins the lab for her PhD thesis work. Welcome, Jun and Trishna!
Jun Kim joins the lab as a postdoctoral fellow and Trishna Patel joins the lab for her PhD thesis work. Welcome, Jun and Trishna!
Jun joins us following completion of his PhD at UC Berkeley in Abby Dernburg's lab, where he developed a high-throughput screening pipeline for regulators of meiosis in C. elegans and characterized novel meiotic regulators, among other projects.
Trishna graduated from UC Berkeley and subsequently worked as a Junior Specialist in the Brain Tumor Center at UCSF before joining the BMS graduate program.
Welcome, Jun and Trishna!!
We are grateful to the Kinship Foundation for the support of our work and excited to join the Searle community!
June 2024
Sonal Joshi joins the lab as a postdoctoral fellow, Madeline McCanne joins the lab for her PhD thesis work, and Annika Bai joins as a summer intern. Welcome, all!
Sonal Joshi joins the lab as a postdoctoral fellow, Madeline McCanne joins the lab for her PhD thesis work, and Annika Bai joins as a summer intern. Welcome, all!
Sonal joins us following completion of her PhD at ICGEB in Trieste, Italy in Federica Benvenuti's lab, where she worked on mechanisms of macrophage recognition of cancer cells.
Madeline graduated from Cornell and subsequently worked as a Research Technician at Massachusetts General Hospital before joining the BMS graduate program.
Annika is a sophomore at UC Santa Barbara and has conducted research at Stanford, Jackson Labs, and UCSB. She joins us through the Emerson Collective First-Gen Interns program.
Welcome, Sonal, Madeline, and Annika!!!
The lab also receives funding from the Helen Diller Family Comprehensive Cancer Center through their Cancer Immunology and Immunotherapy pilot grant program and a Hevolution Foundation Gerosciences Research Opportunities Grant.
January 2024
Jinglin Zhu joins the lab as a postdoctoral fellow, and Trishna Patel starts her rotation. Welcome!
Jinglin Zhu joins the lab as a postdoctoral fellow, and Trishna Patel starts her rotation. Welcome!
Jinglin joins us following completion of his PhD at the Chinese Academy of Sciences in Beijing in Xun Huang's lab, where he worked on mechanisms of lipid regulation and ferroptosis in C. elegans.
Trishna graduated from UC Berkeley and subsequently worked as a Junior Specialist in the Brain Tumor Center at UCSF before joining the BMS graduate program.
Welcome, Jinglin and Trishna!!
The lab also is grateful to receive additional funding support including a Longevity Impetus grant and a New Frontiers Award from the Sandler Program for Breakthrough Biomedical Research.
October 2023
Ariana Sanchez joins the lab as the lab's first postdoctoral fellow. Welcome!
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 in Jessica Feldman's lab, where she established proximity labeling methods in living organisms. Welcome, Ariana!
The lab is also grateful to receive additional funding support from the Larry L. Hillblom Foundation, the Glenn Foundation/AFAR, the 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!
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
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