Lab Dinner 2014
Lab Dinner 2014

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Aghi Lab in Diller Building
Aghi Lab in Diller Building

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Super Bowl Party 2022
Super Bowl Party 2022

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Lab Dinner 2014
Lab Dinner 2014

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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.

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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.

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Neutrophils in Glioblastoma

We have defined pro-tumoral functions of neutrophils in glioblastoma, which we are working to inhibit in preclinical models.

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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.

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Published Work

The Fruits of Our Labor

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

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Manish K. Aghi, MD PhD

Principal Investigator

Harmon Khela

Harmon Khela, BS

Aghi Lab Manager

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Mufeng Hu, PhD

Postdoctoral Fellow

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Jacob Young, MD

Postdoctoral Fellow

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Alex Haddad, MD

Postdoctoral Fellow

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Sabraj Gill, BS

Research Specialist

Atul Saha

Atul Saha, BS

Research Specialist

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Robert Osorio, BS

Medical Student Research Fellow

Meeki Lad

Meeki Lad, BS, MPH

Medical Student Research Fellow

Nikita Choudhary

Nikita Choudhary, BA, MS

Medical Student Research Fellow

Youssef Sibih

Youssef Sibih, BS

Medical Student Research Fellow

Allison Zheng

Allison Zheng, BS

Medical Student Research Fellow

Zain Peeran

Zain Peeran, BS

Medical Student Research Fellow

Luis Carrete

Luis Carrete, BS

Medical Student Research Fellow

Joseph Oh

Joseph Oh, BA

Medical Student Research Fellow

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Isabella Stelter

Undergraduate Research Fellow

Poojan Shukla

Poojan Shukla, BS

Medical Student Research Fellow

 

Previous Lab Newsletters

Circulated every January to collaborators, patient families, and supportive donors.

To subscribe to our newsletter email contact@aghilab.com using the subject "subscribe"

 
 

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 2022

Aghi lab member Elaina Wang wins the Journal of Neuro-Oncology award at the 2022 CNS meeting.

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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.

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UCSF SRTP Poster Session 2019

Joseph Chen presents his poster summarizing work completed in the UCSF Summer Research Training Program (SRTP)

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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

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SNO 2018 Meeting