Parag P. Shah, Ph.D.

Education: Parag P. Shah, Ph.D.

B.Pharm., Institute of Pharmacy (IOP), Nagpur University, India; 1998
M.E. in Biotechnology, Birla Institute of Technology and Science (BITS), Pilanti, Rajasthan, India; July 2001
Ph.D., Industrial Technology Research Centre, Lucknow, India; 2008

Curriculum Vitae: 

Current Positions: 

Assistant Professor, Department of Medicine, Division of Medical Oncology and Hematology, University of Louisville
Member, Experimental Therapeutics Program, Brown Cancer Center 

Contact Information: 

Clinical & Translational Research Building, Rm 220
University of Louisville
505 S. Hancock Street
Louisville, KY 40202 

Phone (502) 852-1172
Fax (502) 852-7979

Email  

Website Link (If applicable): 

Research Description: 

During my Ph.D. work, I explored the fingerprints of Cytochrome P450 genes and their utility as biomarkers of risk and assessment of lung cancer.  Interestingly, I found that along with single nucleotide polymorphisms (SNPs), environmental exposure and gene-environment interactions play important roles in susceptibility of different cancers, including lung and head and neck.  During this period, I also served as an active member of the Indian Genome Variation Consortium. 

Disruption of endoplasmic reticulum (ER) homeostasis leads to ER stress and activation of the unfolded protein response (UPR).  Studies from our lab have shown that ER stress induced epithelial-mesenchymal transition (EMT) in cellular systems and chemotherapeutic drugs commonly used to treat patients also activate ER stress that is associated with activation of an EMT-like state.  Through this mechanism, chemotherapeutic treatment often induces cancer stemness and invasiveness. Currently my area of research focuses on exploring the mechanisms of ER stress induced EMT and important signaling pathways that are involved in cancer progression and metastasis including lung and breast cancer. 

In another research area, I am exploring different biological processes regulated by Ubiquilin proteins and their role in driving cancer progression and tumorigenesis.  The UBQLN proteins comprise five related members: UBQLN1-4 and UBQLNL that all belong to a family of UBL/UBA containing proteins.  These proteins have been shown to be associated with the ubiquitin–proteasome system.  Previous studies from our lab reported that, apart from their role in ER associated degradation (ERAD), they play an important role in EMT in lung adenocarcinoma cells.  Currently my research focusses on exploring the detailed mechanisms by which disruption of the UBQLN-family of proteins contributes to the metastatic progression in a variety of cancers including, lung, breast, and colon. 

Literature Cited (15 Max.): 

  1.  Shah PP, Beverly LJ.  UBQLN family members regulate MYC in lung adenocarcinoma cells.  Cancers2023;15(13):3389.  doi: 10.3390/cancers15133389. PMID: 37444499.  PMCID: PMC10340487 .
  2. Vega AA, Marshall EA, Noonan AJC, Filho FSL, Yang J, Stewart GL, Johnson FD, Vucic EA, Pewarchuk ME, Shah PP, Clem BF, Nislow C, Lam S, Lockwood WW, Hallam SJ, Leung JM, Beverly LJ, Lam WL.  Methionine-producing tumor micro(be) environment fuels growth of solid tumors.  Cellular Oncology (Dordr) 2023 Dec;46(6): 1659-1673.  doi: 10.1007/s13402-023-00832-7.  Epub 2023 Jun 15.  PMID: 37318751.   PMCID: PMC10697899. 
  3. Orwick A, Sears SM, Sharp CN, Doll MA, Shah PP, Beverly LJ, Siskind LJ.  Lung cancer-kidney cross talk induces kidney injury, interstitial fibrosis, and enhances cisplatin-induced nephrotoxicity.  American Journal of Physiology: Renal Physiology 2023 Mar 1;324(3):F287-F300.  doi: 10.1152/ajprenal.00317.2022.  Epub 2023 Feb 2.  PMID: 36727944.  PMCID: PMC9988526 (available on 2024-03-01).
  4. Sears SM, Feng JL, Orwick AJ, Vega AA, Krueger A, Shah PP, Doll MA, Beverly LJ, Siskind LJ.  Pharmacological inhibitors of autophagy have opposite effects in acute and chronic cisplatin-induced kidney injury.  American Journal of Physiology: Renal Physiology 2022 Sep 1;323(3):F288-F298.  doi: 10.1152/ajprenal.00097.2022.  Epub 2022 Jul 7.  PMID: 35796459.  PMCID: PMC9394729.
  5. Doll MA, Ray AR, Salazar-González RA, Shah PP, Vega AA, Sears SM, Krueger AM, Hong KU, Beverly LJ, Hein DW.  Deletion of arylamine N-acetyltransferase 1 in MDA-MB-231 human breast cancer cells reduces primary and secondary tumor growth invivo with no significant effects on metastasis.  Molecular Carcinogenesis 2022 May;61(5):481-493.  doi: 10.1002/mc.23392. Epub 2022 Feb 8.  PMID: 351.33049.  PMCID: PMC9018511 .
  6. Shah PP, Saurabh K, Kurlawala Z, Vega AA, Siskind LJ, Beverly LJ.  Towards a molecular understanding of the overlapping and distinct roles of UBQLN1 and UBQLN2 in lung cancer progression and metastasis.  Neoplasia 2022 Mar;25:1-8.  doi: 10.1016/j.neo.2021.11.010. Epub 2022 Jan 18. PMID: 35063704.  PMCID: PMC8864381.
  7. Sears SM, Dupre TV, Shah PP, Davis DL, Doll MA, Sharp CN, Vega AA, Megyesi J, Beverly LJ, Snider AJ, Obeid LM, Hannun YA, Siskind LJ.  Neutral ceramidase deficiency protects against cisplatin-induced acute kidney injury.  Journal of Lipid Research 2022 Mar;63(3):100179.  doi: 10.1016/j.jlr.2022.100179. Epub 2022 Feb 10.  PMID: 35151662.  PMCID: PMC8953688.
  8. Kurlawala Z, Saurabh K, Dunaway R, Shah PP, Siskind LJ, Beverly LJ.  Ubiquilin proteins regulate EGFR levels and activity in lung adenocarcinoma cells.  Journal of Cellular Biochemistry 2021 Jan;122(1):43-52.  doi: 10.1002/jcb.29830. Epub 2020 Jul 28.  PMID: 32720736.  PMCID: PMC9487017 .
  9. Saurabh K, Shah PP, Doll MA, Siskind LJ, Beverly LJ.  UBR-box containing protein, UBR5, is over-expressed in human lung adenocarcinoma and is a potential therapeutic target.  BMCCancer 2020 Aug 31;20(1):824.  doi: 10.1186/s12885-020-07322-1.  PMID: 32867711.  PMCID: PMC7457484.
  10. Barve A, Vega A, Shah PP, Ghare S, Casson L, Wunderlich M, Siskind LJ, Beverly LJ.  Perturbation of methionine/S-adenosylmethionine metabolism as a novel vulnerability in MLL rearranged leukemia.  Cells 2019 Oct 25;8(11):1322.  doi: 10.3390/cells8111322.  PMID: 31717699.  PMCID: PMC6912509.
  11. Fan TWM, Bruntz RC, Yang Y, Song H, Chernyavskaya Y, Deng P, Zhang Y, Shah PP, Beverly LJ, Qi Z, Mahan AL, Higashi RM, Dang CV, Lane AN.  Denovo synthesis of serine and glycine fuels purine nucleotide biosynthesis in human lung cancer tissues.  Journal of Biological Chemistry 2019 Sep 6;294(36):13464-13477.  doi: 10.1074/jbc.RA119.008743. Epub 2019 Jul 23.  PMID: 31337706.  PMCID: PMC6737211 .
  12. Khan N, Shah PP, Ban D, Trigo-Mouriño P, Carneiro MG, DeLeeuw L, Dean WL, Trent JO, Beverly LJ, Konrad M, Lee D, Sabo TM.  Solution structure and functional investigation of human guanylate kinase reveals allosteric networking and a crucial role for the enzyme in cancer.  Journal of Biological Chemistry2019 Aug 2;294(31):11920-11933.  doi: 10.1074/jbc.RA119.009251.  Epub 2019 Jun 14.  PMID: 31201273.  PMCID: PMC6682748.
  13. Kurlawala Z, Dunaway R, Shah PP, Gosney JA, Siskind LJ, Ceresa BP, Beverly LJ.  Regulation of insulin-like growth factor receptors by Ubiquilin1.  BiochemicalJournal 2017 Dec 6;474(24):4105-4118.  doi: 10.1042/BCJ20170620.  PMID: 29054976.  PMCID: PMC5842694.
  14. Dupre TV, Doll MA, Shah PP, Sharp CN, Siow D, Megyesi J, Shayman J, Bielawska A, Bielawski J, Beverly LJ, Hernandez-Corbacho M, Clarke CJ, Snider AJ, Schnellmann RG, Obeid LM, Hannun YA, Siskind LJ.  Inhibiting glucosylceramide synthase exacerbates cisplatin-induced acute kidney injury.  Journal ofLipidResearch2017 Jul;58(7):1439-1452.  doi: 10.1194/jlr.M076745.  Epub 2017 May 10.  PMID: 28490444.  PMCID: PMC5496040 .
  15. Shah PP, Dupre TV, Siskind LJ, Beverly LJ.  Common cytotoxic chemotherapeutics induce epithelial-mesenchymal transition (EMT) downstream of ER stress.  Oncotarget 2017 Apr 4;8(14):22625-22639.  doi: 10.18632/oncotarget.15150.  PMID: 28186986.  PMCID: PMC5410250.


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