romiAssistant Professor

Research Areas
Genomic and Targeted Approaches for Cancer Gene and Therapeutic Target Discovery

Research Interests

Our laboratory focuses on identifying and studying the role of new molecules and pathways that are involved in tumor initiation and progression. Our research program spans several cancer types including melanoma, hepatocellular carcinoma, breast cancer, ovarian cancer and pancreatic cancer. Our long-term goal is to not only identify new molecules and signaling pathways that regulate the disease but also develop more effective and durable cancer therapies.
Cancer is complex disease, which involve alternation of multiple genetic and epigenetic factors and pathways. Because of its complex nature and the ability of cancer cells to evolve rapidly undertreatment, cancer treatment with durable outcome is a challenging problem. Therefore, in-depth molecular understanding of cancer initiation and progression is necessary for developing effective therapies. In-order to identify and characterize critical cancer vulnerability genes and their downstream network we use genomic and targeted approaches as well employ large scale next generation-based approaches for comprehensive transcriptome as well as proteome analysis. Below, described are the three key areas of our research.

Large-scale Functional Genomics Screens to Identify Tumor Suppressors and Oncogenes

Tumor suppressor genes and oncogenes are two key classes of genes that are shown to have important roles in cancer growth and progression. Most cancers show activation of multiple oncogenes and inactivation of many tumor suppressor genes. Our goal is to identify new tumor suppressor genes and oncogenes via functional genomics approaches of shRNA, CRISPR/CAS9-based and/or ORFome-based library screening. Using one such genome-scale mouse tumorigenesis-based shRNA screening approach, we identified 24 putative tumor suppressor genes (TSGs) that were significantly down regulated in human lung squamous cell carcinomas (hLSCC) (Lin et. al., Cancer Discovery, 2014). 17 out of these 24 genes encoded repressors of FGFR signaling. Amplification of Fibroblast Growth Factor Receptor 1 (FGFR1) is one of mechanisms by which FGFR signaling is upregulated in hLSCCs. Our study identified a new mechanism of FGFR activation, which is independent of FGFR1 amplification, and is dependent upon the loss of repressors of FGFR signaling.

Similarly, by analyzing The Cancer Genome Atlas (TCGA) dataset for high-grade serous ovarian cancer (HGS OvCa) and follow-up functional studies we identified and demonstrated that serine hydroxymethyl transferase 1 (SHMT1) is necessary for ovarian cancer growth and progression (Gupta et. al., Oncogene, 2017). 
Furthermore, recently using a chromatin modifier shRNA library, we performed the shRNA screen in BRAF-mutant melanoma cells and identified BOP1 as a gene whose loss resulted in resistance to BRAF inhibitor treatment in melanoma (Gupta et. al., PNAS, 2019). We interestingly found that in melanoma patients when they become resistant to BRAF inhibitor treatment, BOP1 expression is decreased. Thus, BOP1 levels are indicative of response to BRAF inhibitor-based therapy and serve as an excellent biomarker to identify the patients if they will respond to BRAF-targeted therapies. 
Based on the success of these studies, our lab currently is employing functional genomics screening-based approaches to identify new TSGs and oncogenes in other cancer types. We are also using this to identify factor that cause resistance to current precision cancer therapies. These screens utilize both in vitro and in vivo approaches using both human and mouse model-based systems.

Determining Mechanisms of Oncogenes and Tumor Suppressors Action

The second important objective of my lab is to determine how certain oncogenes and tumor suppressor genes function to drive cancer initiation and progression. For example, we have shown that an interferon stimulated gene IFI6 is necessary for NRAS-induced cellular transformation and for maintaining the growth of NRAS-mutant melanoma. We found that IFI6 via transcription factor E2F2 regulates DNA replication stress and thereby regulating the ability of NRAS to cause cellular transformation and promote melanoma growth (Gupta et. al., ELife, 2016). 

Similarly, we also identified that LKB1 functions as tumor suppressor by regulating genome integrity of cells. Previous studies have shown LKB1 major downstream target is AMP kinase (AMPK). We discovered that LKB1 regulates genome integrity by regulating the BRCA1 mRNA levels via the action of a RNA-binding protein called HuR. These studies established that LKB1 is an integral part of DNA damage/DNA repair pathway and provide a new mechanism by which mutations or deletion of LKB1 may cause early predisposition to a variety of cancer (Gupta et. al., Nucleic Acids Research, 2015).

In yet another study, we discovered that PTEN in part functions as a tumor suppressor by promoting host immune response. Follow up studies form other groups have confirmed our findings and shown that PTEN and PI3K pathway also affect T-cell based immunotherapies (Gupta et. al., Oncogene, 2014).
My laboratory continues to study the mechanism-of-action of newly identified and poorly characterized tumors suppressor genes and oncogenes and elucidate their role in promoting cancer growth and proliferation.

Targeting Cancer Vulnerability Genes and Pathway for Improving Cancer Treatment

Due to complex nature of cancer, achieving durable and effective response to the treatment in most cancers has been a difficult goal. Therefore, there is urgent need to develop new and effective therapeutic approaches for successful cancer treatment. Thus, identifying new drug targets and improving the existing therapeutic approaches to make them more effective is important for developing next generation of cancer therapies. One of the goals of my laboratory is to target cancer vulnerability genes to develop more effective cancer therapy. 
For example, in a previous study we have developed a new combination therapy where we combined CDKN1A (p21) inhibitor along with GRN163L, an inhibitor of RNA component of telomerase and found it to be more effective in inducing apoptosis in cancer cells compared to GRN163L alone (Gupta et. al., PNAS, 2014). Because telomerase is overexpressed in over 90% of cancer cells and single agent telomerase-based therapy is not as effective, this combinatorial treatment is expected to successfully impact treatment of a large percentage of human cancers with telomerase overexpression. Recently, we have also identified IL8 as a biomarker that could effectively predict response to telomerase-based therapy (Solomon et. al., BMC Cancer, 2018). Similarly, our studies have also shown that targeting IFI6-mediated DNA replication stress pathways can be harnessed to potentially treat NRAS mutant melanoma, for which there is no are effective therapies (Gupta et. al., ELife, 2016). Furthermore, our finding discovered that SHMT1 drives sialic acid pathway in ovarian cancer and this pathway can be targeted to treat ovarian cancer (Gupta et. al., Oncogene, 2017). We are currently working to test targeting of this pathway for ovarian cancer treatment using various mouse models of ovarian cancer.
Overall, in this direction my lab continues to identify new cancer targets and test their potential clinical utility using pre-clinical mouse models of cancer with the goal of providing effective cancer therapy.


Graduate School
Max Planck Institute for Molecular Genetics, Berlin, Germany

Postdoctoral fellowship
Yale University, New Haven, Connecticut



Kaul Human Genetics Building
Room 540B
720 20th Street South
Birmingham, AL 35294-0024

(205) 934-4753