Research Area Affiliations
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.
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.