Molecular Pharmacology Program
The Karuna Ganesh Lab
Metastasis causes >90% of cancer death. The emergence, persistence, therapy resistance and lethality of metastatic cancer is driven by dynamic and tenacious metastasis stem cells (MetScs). The Ganesh lab focuses on understanding the molecular mechanisms that underlie the emergence of regenerative plasticity during metastasis. We employ cutting edge patient-derived organoid and mouse models of colorectal cancer, transcriptomic, epigenomic and single cell approaches, and mechanistic studies to: (1) elucidate how tumor invasion and dissemination induce phenotypic plasticity enabling the emergence of pro-metastatic regenerative traits (2) dissect the role of stromal cells, including immune cells, in promoting and constraining MetSC plasticity (3) define key signaling nodes that drive MetSC plasticity and develop therapeutic strategies for targeting such vulnerabilities and (4) collaborate with clinicians to understand mechanisms of therapy resistance in metastasis.
Ganesh K, Basnet H, Laughney AM, Kaygusuz Y, He L, O’Rourke KP, Reuter V, Huang YH, Er EE, Masilionis I, Weiser MR, Saltz LB, Garcia-Aguilar J, Koche R, Lowe SW, Pe’er D, Shia J, Massagué J. L1CAM marks the regenerative origin of metastasis stem cells in colorectal cancer. Nature Cancer. 1, 28–45 (2020). https://doi.org/10.1038/s43018-019-0006-x
Ganesh K, Wu C, O’Rourke KP, Adileh M, Szeglin B, Wasserman I, Marco MR, Shady M, Zheng Y, Karthous WR, Won HH, Choi SH, Pelossof RA, Barlas A, Pappou E, Elghouayel A, Strong JD, Chen CT, Harris JW, Wiser MR, Nash GM, Guillem JG, Wei IH, Cercek A, Kolesnick RN, Manova-Todorova KO, Saltz LB, DeMatteo RP, Massague J, Romesser PB, Paty PB, Yaeger RD, Clevers H, Berger M, Shia J, Lowe SW, Dow LE, Garcia-Aguilar J, Sawyers CL, Smith JJ. A rectal cancer model establishes a platform to study individual responses to chemoradiation. Nature Medicine. 2019 Oct;25(10):1607-1614. doi: 10.1038/s41591-019-0584-2. Epub 2019 Oct 7. PubMed PMID: 31591597.
Ganesh K, Stadler ZK, Cercek A, Mendelsohn RB, Shia J, Segal NH, Diaz LA Jr. Immunotherapy in colorectal cancer: rationale, challenges and potential. Nature Reviews Gastroenterology Hepatology. 2019 Jun;16(6):361-375. doi: 10.1038/s41575-019-0126-x. Review. PubMed PMID: 30886395.
Datta J, Smith JJ, Chatila WK, McAuliffe JC, Kandoth C, Vakiani E, Frankel TL, Ganesh K, Wasserman I, Lipsyc-Sharf M, Guillem J, Nash GM, Paty PB, Weiser MR, Saltz LB, Berger MF, Jarnagin WR, Balachandran V, Kingham TP, Kemeny NE, Cercek A, Garcia-Aguilar J, Taylor BS, Viale A, Yaeger R, Solit DB, Schultz N, D’Angelica MI. Co-Altered Ras/B-raf and TP53 is Associated with Extremes of Survivorship and Distinct Patterns of Metastasis in Metastatic Colorectal Cancer Patients. Clin Cancer Res. 2019 Nov 12. pii: clincanres.2390.2019. doi: 10.1158/1078-0432.CCR-19-2390. [Epub ahead of print] PubMed PMID: 31719050.
Wang T, Lee LH, Vyas M, Zhang L, Ganesh K, Firat C, Segal NH, Desai A, Hechtman JF, Ntiamoah P, Weiser MR, Markowitz AJ, Vakiani E, Klimstra DS, Stadler ZK, Shia J. Colorectal carcinoma with double somatic mismatch repair gene inactivation: clinical and pathological characteristics and response to immune checkpoint blockade. Mod Pathol. 2019 Jun 7. doi: 10.1038/s41379-019-0289-6. [Epub ahead of print] PubMed PMID: 31175329.
Karuna Ganesh, MD, PhD
- Physician-scientist Karuna Ganesh studies stem cell plasticity in metastasis, therapy resistance and tissue regeneration.
- MD, PhD, University of Cambridge (UK)
- Damon Runyon Clinical Investigator Award (2019)
- Burroughs Wellcome Career Award for Medical Scientists (2019)
- Josie Robertson Investigator (2019)
- NIH/NCI K08 Clinician Scientist Career Development Award (2018)
- Investigator, Stand Up to Cancer Colorectal Cancer Dream Team (2017)
- American Cancer Society Postdoctoral Fellowship (2017)
- Shulamit Katzman Endowed Postdoctoral Fellowship (2017)
- Conquer Cancer Foundation of ASCO Young Investigator Award (2016)
- AACR Basic Cancer Research Fellowship (2016)
- MRC-LMB PhD Scholarship (2006)
- Gates Cambridge Scholarship (2004)
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Doctors and faculty members often work with pharmaceutical, device, biotechnology, and life sciences companies, and other organizations outside of MSK, to find safe and effective cancer treatments, to improve patient care, and to educate the health care community.
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Karuna Ganesh discloses the following relationships and financial interests:
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