Kavita Shah

Active Mentor - currently hosting PULSe students for laboratory rotations and recruiting PULSe students into the laboratory; serves on preliminary exam committees

Current Research Interests:

Our research goal is to develop and apply chemical tools to dissect biological pathways. We specifically focus on Protein Kinase and G Protein superfamilies. Protein Kinases are a large family of signaling proteins (538 kinases have been discovered in human genome). Deregulated kinase signaling is implicated in more than 400 diseases including cancer, neurological diseases, metabolic diseases, rheumatoid arthritis, cardiovascular diseases and psoriasis. Similarly, Guanine nucleotide binding proteins (G Proteins) constitute another large family of signaling proteins (220 members) that are finely interwoven in every aspect of cellular signaling. Ras, the founding member of this family, is implicated in more than 30-40% of all known human cancers. Our research group is deeply interested in unraveling the molecular mechanisms of cancer and neurodegeneration in cells, animal models and human diseased tissues, with the goal of identifying novel therapeutic targets, which can be targeted independently or in combination to prevent or treat human diseases. To this end, we employ a combination of chemical, genetic, genomic and proteomic approaches.

Our research activities generally fall into three categories: (1) Exploring the mechanism of neurodegeneration in Alzheimer’s disease for developing mechanism-based therapies. (2) Identification and Validation of Novel Therapeutic Targets in cancer, particularly those proteins which are cancer-specific. (3) Development of Chemical Tools for dissecting signaling pathways in cells. We are also involved in the synthesis and screening of small molecules which can potentially act as anti-cancer agents directed towards specific targets in cells.

Selected Publications:

1. Sooreshjani MA, Kamra M, Zoubeidi A, Shah K*. (2021) Reciprocal deregulation of NKX3.1 and AURKA axis in castration-resistant prostate cancer and NEPC models. J Biomed Sci. 28(1), 68.

2. Sooreshjani MA, Nikhil K, Kamra M, Nguyen D, Kumar D, Shah K*. (2021) LIMK2-NKX3.1 Engagement Promotes Castration Resistant Prostate Cancer. Cancers (Basel) 13(10), 2324.

3. Nikhil K, Haymour HS, Kamra M, Shah K*. (2021) Phosphorylation-Dependent Regulation of SPOP by LIMK2 Promotes Castration Resistant Prostate Cancer. British J Cancer 124(5), 995-1008.

4. Nikhil K, Kamra M, Raza A, Shah K*. (2021) Negative cross talk between LIMK2 and PTEN promotes castration resistant prostate cancer pathogenesis in cells and in vivo. Cancer Lett 498, 1-18. doi: 10.1016/j.canlet.2020.09.010.

5. Nikhil K, Kamra M, Raza A, Haymour HS, Shah K*. (2020) Molecular Interplay between AURKA and SPOP dictates CRPC Pathogenesis via Androgen Receptor. Cancers 12(11), 3247. doi: 10.3390/cancers12113247.

6. Nikhil K, Raza A, Haymour HS, Flueckiger BV, Chu J, Shah K*. (2020) Aurora Kinase A-YBX1 Synergy Fuels Aggressive Oncogenic Phenotypes and Chemoresistance in Castration-Resistant Prostate Cancer. Cancers 12(3), 660. doi: 10.3390/cancers12030660.

7. Nikhil K, Chang L, Viccaro K, Jacobsen M, McGuire C, Satapathy SR, Tandiary M, Broman MM, Cresswell G, He YJ, Sandusky GE, Ratliff TL, Chowdhury D, Shah K*. (2019) Identification of LIMK2 as a therapeutic target in castration resistant prostate cancer. Cancer Lett. 448, 182-196.

8. Nikhil K, Viccaro K, Shah K*. (2018) Multifaceted Regulation of ALDH1A1 by Cdk5 in Alzheimer's disease. Mol Neurobiol. 56(2), 1366–1390.

9. Nikhil K, Shah K*. (2017) The Cdk5-Mcl-1 axis promotes mitochondrial dysfunction and neurodegeneration in a model of Alzheimer's disease. J Cell Sci. 130(18), 3023-3039.

10. Wang J, Nikhil K, Viccaro K, Lei C, White J, Shah K*. (2017) Phosphorylation-dependent Regulation of ALDH1A1 by Aurora Kinase A: Insights on their Synergistic Relationship in Pancreatic Cancer. BMC Biology 15(1), 1-10. doi: 10.1186/s12915-016-0335-5.

11. Wang J, Nikhil K, Viccaro K, Lei C, Jacobsen M, Sandusky G, Shah K*. (2017) Aurora A-Twist1 Axis Promotes Highly Aggressive Phenotypes in Pancreatic Carcinoma. J Cell Sci. 130(6), 1078-1093. doi: 10.1242/jcs.196790.

12. Sun KH, de Pablo Y, Vincent F, Johnson EO, Chavers AK, Shah K*. (2008) Novel Genetic Tools Reveal Cdk5's Major Role in Golgi Fragmentation in Alzheimer's Disease.Mol Biol Cell. 19(7), 3052-69.

13. Sun KH, de Pablo Y, Vincent F, Shah K*. (2008) Deregulated Cdk5 Promotes Oxidative Stress and Mitochondrial Dysfunction.J Neurochem. 107, 265-278.

14. Vincent F, Cook S, Johnson EO, Emmert D, Shah K*. (2007) Engineering Unnatural Nucleotide Specificity to Probe G protein SignalingChem Biol 14(9), 1007-18. (Research Highlights: Stevens K. (2007) Designer Modulators Nature Methods 4(12), 988.