Srinivas Vinod Saladi, Ph.D.

Harvard Medical School

Instructor in Otolaryngology

Massachusetts Eye and Ear

Investigator

Research Summary

Research Area Affiliations 

 

Research Summary 

Dr. Saladi’s research interests primarily focus on understanding the mechanism by which epigenetic reprogramming contributes to cellular plasticity in tumors. His research aims to define the mechanisms in which deregulated chromatin remodeling or altered chromatin landscape act as oncogenic drivers in cancer. Epigenetic reprogramming is a key oncogenic driver event in multiple cancers, however very little is known about the deregulated epigenetic programs in head and neck squamous cell carcinomas (HNSCC). 

Dr. Saladi had identified ACTL6A, subunit of SWI/SNF chromatin remodeling enzymes as a novel, amplified, and driver oncogene in majority of HNSCC driving regenerative proliferation and poor prognosis in patients. This was the first report of a chromatin factor as a driver oncogene in solid tumors. Traditionally, SWI/SNF complex was considered as a tumor suppressor with the complex sub units being mutated in 20 percent of human cancers. Dr. Saladi is one of the few researchers that discovered an oncogenic role of SWI/SNF complex in tumors. 

His research interests also include delineating the oncogenic role of hippo signaling pathway effector, YAP1 in squamous cell carcinomas. Hippo pathway was shown to bypass the MAPK oncogenic addiction in advanced stage of multiple cancers contributing to cancer progression. Dr. Saladi has unraveled the oncogenic role of Hippo pathway in HNSCC. He had identified WWC1 and GPRC5A (upstream inhibitors of oncogenic YAP1 activity) as repressed in HNSCC, thereby promoting tumorigenesis and conferring poor prognosis in a subset of HNSCC patients. 

Collectively, Dr. Saladi integrates genomics, epigenetics, and signaling to dissect the mechanisms contributing to head and neck cancer maintenance and progression.

 

Select Publications 

Developmental history provides a roadmap for the emergence of tumor plasticity. Tata PR, Chow RD, Saladi SV, Tata A, Konkimalla A, Bara A, Montoro D, Hariri LP, Shih A, Mino-Kenudson M, Mou H, Kimura S, Ellisen LW, Rajagopal J. Dev Cell. 2018;(44):679–93.

Clinical genotyping reveals expressed gene fusions as frequent drivers of poor outcomes in hormone receptor positive creast cancer. Matissek KJ, Onozato ML, Sun S, Zheng Z, Schultz A, Lee J, Patel K, Jerevall PL, Saladi SV, Macleay A, et al. Cancer Discovery. 2018;(3):336–53. 

ACTL6A is co-amplified with p63 in squamous cell carcinoma to drive YAP activation, regenerative proliferation and poor prognosis. Saladi SV, Ross K, Karaayvaz M, Tata PR, Hongmei M, Rajagopal J, Ramawamy S, Ellisen LW. Cancer Cell. 2017;(31):35–49.  

Genomics, Personalized Medicine and Oral Disease. Saladi SV, Ellisen LW. Oral Cancer. Springer Edition 2015; 293–309. 

BRG1 promotes survival of UV-irradiated melanoma cells by cooperating with MITF to activate the melanoma inhibitor of apoptosis gene. Saladi SV, Wong P, Trivedi A, Marathe H, Keenen B, de la Serna IL. Pigment Cell and Melanoma Res. 2013;26(3):377–91.

Biosketch

Education 

BS, Biochemistry, Microbiology, and Aquaculture, Nagarjuna University, 2000
MS, Integrated Biology, Madurai Kamaraj University, 2002
PhD, Biochemistry and Cancer Biology, University of Toledo, College of Medicine, 2011


Postgraduate Training 

2011–2017: Post-doc, Cancer Epigenetics and Signaling, MGH Cancer Center/Harvard Medical School


Awards and Honors (select)

2011: Dean’s Award for Outstanding Graduating PhD Student, University of Toledo College of Medicine
2016: Faculty of 1000 (F1000) Best Presentation Award, 7th International p63/p73 Workshop
2017: Douglass Family Foundation Prize for Excellency in Hematology-Oncology Laboratory, MGH Cancer Center
2018: Poster of Distinction, MGH Scientific Advisory Committee Meeting


Editorial Roles

2014–Present: Editorial Board/Reviewer, PLoS One
2015–Present: Editorial Board/Reviewer, BMC Genomics and Cancer Letters
2018–Present: Editorial Board/Reviewer, PeerJ and Frontiers in Cell and Developmental Biology