The Aghi Lab
What We Do
The Aghi lab investigates the tumor microenvironment of malignant brain tumors like glioblastoma or brain metastases and benign brain tumors like pituitary adenomas. We use techniques such as single cell sequencing, novel xenograft models, and collaborations with industry partners to investigate the role of the tumor microenvironment in the aggressive biology and therapeutic resistance of these tumors. Our research is generously supported by funding from the NIH and a number of private foundations and philanthropic sources.
Areas of Research in the Aghi Lab
Just a few examples of areas of active study in the Aghi lab
c-Met/beta1 integrin complex in glioblastoma and metastases
We have identified a structural complex between c-Met and beta1 integrin that drives invasive resistance in glioblastoma and metastatic spread of cancer. Current work seeks to identify small molecule inhibitors blocking the formation of this complex.
Cancer-Associated Fibroblasts in Glioblastoma
We have used single cell RNA-seq and spatial transcriptomics to identify cancer-associated fibroblasts in the perivascular niche of glioblastoma. We also defined a role for GBM stem cells in attracting these cells, and numerous pro-humoral functions of these fibroblasts.
Neutrophils in Glioblastoma
We have defined pro-tumoral functions of neutrophils in glioblastoma, which we are working to inhibit in preclinical models.
3D Bioengineered Models to Study GBM Invasion
We have partnered with the Kumar lab in the UC Berkeley bioengineering department to use 3D tissue models for screening of druggable mediators of invasion and invasive resistance in glioblastoma.
Published Work
The Fruits of Our Labor
Jain S, Rick JW, Joshi RS, Beniwal A, Spatz J, Gill S, Chang A, Choudhary N, Nguyen AT, Sudhir S, Chalif E, Chen JS, Chandra A, Haddad AF, Wadhwa H, Shah SS, Choi S, Hayes J, Wang L, Yagnik G, Costello JF, Diaz A, Heiland DH, Aghi MK. Identification of Cancer-Associated Fibroblasts in Glioblastoma and Defining Their Pro-tumoral Effects. Journal of Clinical Investigation, in press.
Safaee MM, Wang EJ, Jain S, Chen J-S, Gill S, Garcia JH, Beniwal AS, Nguyen AT, Maclean JM, Wycoff K, Aghi MK. CD97 is associated with mitogenic pathway activation and immune microenvironment changes in glioblastoma. Scientific Reports, in press.
Lau D, Wadhwa H, Sudhir S, Jain S, Chandra A, Nguyen A, Spatz J, Shah SS, Cheng J, Safaee M, Yagnik G, Jahangiri A, Aghi MK. Role of c-Met/ß1 integrin complex in the metastatic cascade in breast cancer. JCI Insight, in press.
Haddad AF, Chen JS, Oh T, Pereira MP, Joshi RS, Aghi MK. Higher cytolytic score correlates with an immunosuppressive tumor microenvironment and reduced survival in glioblastoma. Scientific Reports 10: 17580. 2020.
Chandra A, Jahangiri A, Chen W, Nguyen AT, Yagnik G, Pereira MP, Jain S, Garcia JH, Shah SS, Wadhwa H, Joshi RS, Weiss J, Wolf KJ, Lin J-M G, Mueller S, Rick JW, Diaz AA, Gilbert LA, Kumar S, Aghi MK. Clonal ZEB1-driven mesenchymal transition promotes targetable oncologic anti-angiogenic therapy resistance. Cancer Research 80: 1498-1511. 2020.
Yagnik G, Rutkowski M, Shah S, Aghi MK. Stratifying nonfunctional pituitary adenomas into two groups distinguished by macrophage subtypes. Oncotarget 10: 4350, 2019.
Jahangiri A, Sidrov M, Han SW, Mascharak S, De Lay M, Wagner JR, Castro BA, Imber BS, Lu K, Bergers G, Weiss WA, Aghi MK. c-Met/β1 integrin: A cross-activating c-Met/β1 integrin complex drives metastasis and invasive resistance in cancer. Proceedings of the National Academy of Sciences 114: E8685-E8694. 2017.
Yagnik G, Jahangiri A, Chen R, Wagner JR, Aghi MK. Role of a p53 polymorphism in the development of nonfunctional pituitary adenomas. Molecular and Cellular Endocrinology 446: 81-90. 2017.
Kuang R, Jahangiri A, Mascharak S, Nguyen A, Chandra A, Flanigan PM, Yagnik G, Wagner JR, De Lay M, Carrera D, Castro BA, Hayes J, Sidorov M, Garcia J, Eriksson P, Ronen S, Phillips J, Molinaro A, Koliwad S, Aghi MK. GLUT3 upregulation promotes metabolic reprogramming associated with anti-angiogenic therapy resistance. JCI Insight 2:e88815. 2017.
Castro BA, Flanigan P, Jahangiri A, Kuang R, De Lay M, Chen W, Yagnik G, Mascharak S, Sidorov M, Wagner JR, Shrivastav S, Kohanbash G, Okada H, Aghi MK. Downregulation of macrophage migration inhibitory factor causes oncologic therapeutic resistance. Oncogene 36: 3749-3759. 2017.
Carbonell WS, De Lay M, Jahangiri A, Park C, Aghi MK. Targeting Beta1 Integrin Potentiates Bevacizumab Therapy and Inhibits Growth of Bevacizumab-Resistant Glioblastoma Multiforme. Cancer Research 73: 3145-3154. 2013. (image from article featured in full size on cover of Cancer Research)
Jahangiri A, Carbonell WS, De Lay M, Hu Y-L, Lu K, Paquette J, Tokuyasu TA, Tsao S, Chaumeil MM, Ronen SM, Bergers G, Aghi MK. Gene expression profile identifies mesenchymal tyrosine kinase c-Met as a targetable mediator of anti-angiogenic therapy resistance. Clinical Cancer Research 19: 1773-1783. 2013. (with a commentary by Joseph H. McCarty. Glioblastoma resistance to anti-VEGF therapy: has the challenge been MET?. Clinical Cancer Research 19: 1631-1633. 2013).
De Lay M, Jahangiri A, Carbonell WS, Hu Y-L, Tsao S, Tom MW, Paquette J, Tokuyasu TA, Aghi MK. Microarray analysis verifies two distinct phenotypes of glioblastomas resistant to anti-angiogenic therapy. Clinical Cancer Research 18: 2930-2942, 2012.
Hu YL, Jahangiri A, DeLay M, Aghi MK. Tumor cell autophagy as an adaptive response mediating resistance to treatments like anti-angiogenic therapy. Cancer Research 72: 4294-4299. 2012.
People
Manish K. Aghi, MD PhD
Principal Investigator
Harmon Khela, BS
Aghi Lab Manager
Mufeng Hu, PhD
Postdoctoral Fellow
Jacob Young, MD
Postdoctoral Fellow
Alex Haddad, MD
Postdoctoral Fellow
Sabraj Gill, BS
Research Specialist
Atul Saha, BS
Research Specialist
Robert Osorio, BS
Medical Student Research Fellow
Meeki Lad, BS, MPH
Medical Student Research Fellow
Nikita Choudhary, BA, MS
Medical Student Research Fellow
Youssef Sibih, BS
Medical Student Research Fellow
Allison Zheng, BS
Medical Student Research Fellow
Zain Peeran, BS
Medical Student Research Fellow
Luis Carrete, BS
Medical Student Research Fellow
Joseph Oh, BA
Medical Student Research Fellow
Isabella Stelter
Undergraduate Research Fellow
Poojan Shukla, BS
Medical Student Research Fellow
Previous Lab Newsletters
Circulated every January to collaborators, patient families, and supportive donors.
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Aghi Lab Journal Covers
Over the years we've been fortunate to have some of our work featured on the covers of journals.
Cancer Research
May 2013
This cover art illustrates immunostaining showing unregulated perivascular beta1 integrin expression in glioblastomas resistant to anti-angiogenic therapy
Seminars In Cancer Biology
November 2020
This cover art illustrates mechanisms of resistance to anti-angiogenic therapy.
Journal of Neuro-Oncology
February 2021
This cover art illustrates convection-enhanced delivery of drugs to glioblastoma.
Journal of Neuro-Oncology
March 2021
This cover illustration demonstrates mechanisms of interaction between viral therapies and immunotherapy for glioblastoma.
Lab Photo Album
Aghi Lab At Work and Play Over the Years
CNS Meeting 2023
Aghi lab member Nikita Choudhary wins the Stache Strong award at the at the 2023 CNS meeting.
CNS Meeting 2022
Aghi lab member Elaina Wang wins the Journal of Neuro-Oncology award at the 2022 CNS meeting.
EANO Meeting 2022
Meeki Lad was awarded the SNO-EANO travel scholarship allowing him to present his work on tumor-associated neutrophils at the 2022 EANO meeting in Vienna.
UCSF SRTP Poster Session 2019
Joseph Chen presents his poster summarizing work completed in the UCSF Summer Research Training Program (SRTP)
ASCI 2019 Meeting
Sumedh Shah presents his work on tumor-associated neutrophils done as part of an HHMI fellow at the 2019 ASCI meeting in Chicago
SNO 2018 Meeting
Members of the Aghi lab giving talks at the Society for Neuro-Oncology 2018 annual meeting in New Orleans gather outside the lecture hall
UCSF PhD Graduation 2018
Aghi lab member Arman Jahangiri gathers with the lab after earning his PhD through the Biomedical Sciences (BMS) graduate division at UCSF
San Francisco Giants Game 2018
The nice part about having a lab walking distance from a baseball stadium is the chance for the lab to catch a ball game. Hoping to do the same when the Warriors stadium opens in fall 2019.
SNO 2017 Meeting
Ankush Chandra stands next to his award winning poster from the 2017 Society for Neuro-Oncology (SNO) Annual Meeting in San Francisco
SNO 2016 Meeting
Postdoctoral fellow Garima Yagnik stands by her poster which won best poster at the 2016 Society for Neuro-Oncology (SNO) Annual Meeting
AANS Meeting 2013
Arman Jahangiri winning the Integra Foundation Award for his research on pituitary tumors at the 2013 AANS Annual Meeting
Lab Alumni
Garima Yagnik, PhD
Postdoctoral Fellow 2014-2019
After completing her postdoctoral fellowship in the Aghi Lab, Garima became a Senior Scientist at Allogene, where she works on CAR-T cell therapies.
W. Shawn Carbonell, MD PhD
Postdoctoral Fellow 2010-2012
After completing his postdoctoral fellowship in the Aghi lab, Shawn has gone on to become founder and Chief Scientific Officer at Oncosynergy, developing integrin blocking antibodies as a therapeutic for cancer.
Arman Jahangiri, MD PHD
HHMI fellow 2011-2013
UCSF PhD student 2013-2018
After completing three years of medical school at UT Southwestern, Arman joined the Aghi lab as a Howard Hughes fellow 2011-2013 and as a BMS graduate student at UCSF 2013-2018. He is currently a neurosurgery resident at Emory University.
Saket Jain, PhD
Postdoctoral Fellow 2019-2022
Saket Jain was an Aghi lab postdoctoral fellow who is now a Senior Scientist at Genentech.
Jordan Spatz, MD PhD
Postdoctoral Fellow 2019-2021
After completing his postdoctoral research in the Aghi lab, Jordan became a surgical intern at Oregon Health Sciences.
Michael Safaee, MD
Post-Doctoral Fellow 2018-2019
Mike completed a postdoctoral fellowship funded by an F32 grant from the NIH and a Neurosurgery Research Education Foundation (NREF) Fellowship.
Taemin Oh, MD
Postdoctoral Fellow 2019-2020
Taemin Oh completed a yearlong research fellowship and is completing his neurosurgery residency at UCSF.
Ramin Morshed, MD
Postdoctoral Fellow 2020-2021
Ramin Morshed completed a yearlong postdoctoral fellow and is now completing his neurosurgery residency at UCSF.
Darryl Lau, MD
Postdoctoral Fellow 2017-2018