EducationPh.D. in Molecular & Cellular Biology, Baylor College of Medicine (BCM), Houston, Texas
B.A. in Biology and Chemistry, Austin College, Sherman, Texas
Dr. Shafi’s research is focused on defining the mechanisms and biomarkers of therapeutic resistance in patients with advanced prostate cancer (PCa) with the goal to develop better treatment strategies. PCa is an androgen-dependent disease. Metastatic PCa is treated with androgen deprivation therapy (ADT); although initially effective, tumors recur after 2-3 years and are then termed castration-resistant prostate cancer (CRPC). Intriguingly, CRPC remains largely androgen receptor (AR)-dependent, due to aberrant reactivation of AR through multiple distinct mechanisms that promote cell survival and proliferation. Currently, there is no definitive cure for CRPC. Thus, there is a vital need for the development of new avenues of clinical intervention in PCa to improve patient outcome.
Our laboratory encompasses a translational research program that will directly impact the PCa field and advance clinical practice. The ongoing, highly innovative research projects in the laboratory will have significant implications for PCa by defining the biology of aggressive disease and significantly improving our current understanding of therapy resistance.
Utilizing molecular and translational methods, our lab is focused on several avenues of research including:
1) Elucidate novel insight into CRY1 and other circadian factors function in human tumors in order to identify new avenues for therapeutic intervention.
2) Leverage novel patient-derived models to predict therapeutic response in PCa.
3) Discern the impact of co-activators CBP/p300 in disease progression.
In sum, these research projects will support the overarching goal to reduce progression of lethal disease and enhance efficacy of current standard-of-care therapeutics in PCa treatment.
Publication list: https://www.ncbi.nlm.nih.gov/myncbi/collections/mybibliography/
Representative publications, projects, and/or deployments
American Association of Cancer Research (AACR) NextGen Star - 2022
Prostate Cancer Foundation – Young Investigator
Early Career Reviewer, Endocrinology Journal
Shafi AA, McNair CM, McCann JJ, Alshalalfa M, Shostak A, Severson TM, Zhu Y, Bergman A, Gordon N, Mandigo AC, Chand SN, Gallagher P, Dylgjeri E, Laufer TS, Vasilevskaya IA, Schiewer MJ, Brunner M, Feng FY, Zwart W, Knudsen KE. The circadian cryptochrome, CRY1, is a pro-tumorigenic factor that rhythmically modulates DNA repair. Nat Commun. 2021 Jan 15;12(1):401. doi: 10.1038/s41467-020-20513-5. PMID: 33452241; PMCID: PMC7810852.
Shafi AA, Knudsen KE. Cancer and the Circadian Clock. Cancer Res. 2019 Aug 1;79(15):3806-3814. doi: 10.1158/0008-5472.CAN-19-0566. Epub 2019 Jul 12. Review. PubMed PMID: 31300477.
Shafi AA, Schiewer MJ, de Leeuw R, Dylgjeri E, McCue PA, Shah N, Gomella LG, Lallas CD, Trabulsi EJ, Centenera MM, Hickey TE, Butler LM, Raj GV, Tilley WD, Cukierman E, Knudsen KE. Patient-derived Models Reveal Impact of the Tumor Microenvironment on Therapeutic Response. European Urology Oncology. 2018. September. https://doi.org/10.1016/j.euo.2018.04.019
Mandigo AC, Yuan W, Xu K, Gallagher P, Pang A, Guan YF, Shafi AA, Thangavel C, Sheehan B, Bogdan D, Paschalis A, McCann JJ, Laufer TS, Gordon N, Vasilevskaya IA, Dylgjeri E, Chand SN, Schiewer MJ, Domingo-Domenech J, Den RB, Holst J, McCue PA, de Bono JS, McNair C, Knudsen KE. RB/E2F1 as a Master Regulator of Cancer Cell Metabolism in Advanced Disease. Cancer Discov. 2021 Sep;11(9):2334-2353. doi: 10.1158/2159-8290.CD-20-1114. Epub 2021 Apr 20. PMID: 33879449; PMCID: PMC8419081.
McCann JJ, Vasilevskaya IA, McNair C, Gallagher P, Poudel Neupane N, Dean JL, de Leeuw R, Shafi AA, Dylgjeri E, Mandigo AC, Schiewer MJ, Knudsen KE. Mutant p53 elicits context-dependent pro-tumorigenic phenotypes. Oncogene. 2022 Jan;41(3):444-458. doi: 10.1038/s41388-021-01903-5. Epub 2021 Nov 12. PMID: 34773073; PMCID: PMC8755525.
Mandigo AC, Shafi AA, McCann JJ, Laufer TS, Dylgjeri E, Vasilevskaya I, Schiewer MJ, McNair CM, Knudsen KE. Novel Oncogenic Transcription Factor Cooperation in RB-Deficient Cancer. Cancer Res. 2022 Jan 15;82(2):221-234. doi: 10.1158/0008-5472.CAN-21-1159. Epub 2021 Oct 8. PMID: 34625422.
Dylgjeri E, Kothari V, Shafi AA, Gallagher PT, Pang A, Guan YF, Goodwin JF, McCann JJ, Mandigo AC, Chand S, Semenova G, McNair CM, Vasilevskaya I, Schiewer MJ, Lallas C, McCue, Gomella LG, Schaeffer EM, Seifert E, Carroll JS, Holst, Kelly WK, Knudsen KE. Novel Role of DNA-PK in Metabolism: DNA-PK Promotes Glycolysis in Castration Resistance Prostate Cancer. Clin Cancer Res. 2022 Jan 25: clincanres.1846.2021. doi: 10.1158/1078-0432.CCR-21-1846. Epub ahead of print. PMID: 35078861.