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.
Karuna Ganesh, MD, PhD
Research FocusPhysician-scientist Karuna Ganesh studies stem cell plasticity in metastasis, therapy resistance and tissue regeneration.
EducationMD, PhD, University of Cambridge (UK)
- 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. bioRxiv 640193; doi: https://doi.org/10.1101/640193
- 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.
- 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)