Shilpa Dhar
Assistant Professor
The University of Texas MD Anderson Cancer Center at Houston
Department of GI Medical Oncology
In recent years, we have made several discoveries using human-derived samples on various platforms including multi-platform profiling the functional, phenotypic, and spatial heterogeneity of tumor cells and cells of the TIME, delineating tumor cells-of-origin, lineage diversity and plasticity, and analysis of tumor-immune interactions, in particular, using the cutting-edge single cell sequencing technologies coupled with the state-of-the-art computation and modeling (GUT, 2020; Nature Medicine 2021). We also discovered (in my lab) that Yap1 regulates SOX9 and SOX9 induces LIF (which is immune suppressive). Identifying mechanism and novel target in gastric adenocarcinoma: I have joined Dr. Ajani's team, who has set up a comprehensive infrastructure at MDACC to gather patient specimens and clinical data, resulting in numerous translational works and papers.
We have carefully analyzed the mutation rates of various epigenetic modifiers in gastroesophageal cancer and have discovered important results. Most recently, we have demonstrated that YAP1 is highly expressed in malignant cells from peritoneal cavity of GAC patients, and malignant ascites cells with high YAP1 expression are easy to form PDX tumor and PDX-metastasis in mice. Knockout YAP1 in PC cells delayed tumor growth in PDX and blocked peritoneal metastasis in patient-derived orthotopic model.
In addition, YAP1high tumor cells are associated with tumor favoring TME by immune suppression and activation of cancer associated fibroblasts (CAFs). YAP1 mediated gastric adenocarcinoma peritoneal metastases can be attenuated by YAP1 inhibition. Furthermore, we have identified more novel targets by integrated analyses of multiplex profiling (WES, RNAseq, MS-SPEC and Single cell Sequence) of primary and peritoneal carcinomatosis and explore the mechanisms on these targets in mediating GAC cell peritoneal metastases.
Education & Training
PhD - Gujarat University - 1999