A. Personal Statement

Prostate cancer and benign prostatic hyperplasia are two diseases which present a significant burden for older men in the US. Although BPH is not usually life-threatening, the mechanisms contributing to BPH are largely unknown which makes it difficult to develop successful BPH prevention and treatment strategies. I have 16 years research experience in the study of prostate diseases. Most notably, I have expertise in animal modeling, in particular the generation and characterization of the Cdh1 knockout mouse as a model of BPH. Additionally, I have expertise in isolating and culturing various cell types derived from patients with both benign and malignant disease and have successfully utilized these cells in a variety of experiments that are uniquely suited for application to BPH research, including primary cell culture and co-cultures, gene expression analyses, western blotting and immunostaining/immunofluorescent staining. As there are limited animal models of BPH, experiments utilizing patient tissues present a great opportunity to study disease development and progression directly. My goal is to focus my research skills with primary tissues and cultures and animal model development toward determining the association of aging on the etiology of BPH and prostate cancer, to establish a collaborative relationship with urologists and pathologists with the ultimate goal of facilitating the effective translation of my basic research findings into potential prevention and treatment strategies for improving prostate disease patient outcomes.

1. Pascal LE, Wang Y, Zhong M, Wang D, Chakka AB, Yang Z, Li F, Song Q, Rigatti LH, Chaparala S, Chandran U, Parwani AV, Wang Z. EAF2 and p53 Co-Regulate STAT3 Activation in Prostate Cancer. Neoplasia. 2018 Apr;20(4):351-363. PubMed PMID: 29518696; PubMed Central PMCID: PMC5909677.

2. Wang Y, Pascal LE, Zhong M, Ai J, Wang D, Jing Y, Pilch J, Song Q, Rigatti LH, Graham LE, Nelson JB, Parwani AV, Wang Z. Combined Loss of EAF2 and p53 Induces Prostate Carcinogenesis in Male Mice. Endocrinology. 2017 Dec 1;158(12):4189-4205. PubMed PMID: 29029019; PubMed Central PMCID: PMC5711381.

3. O'Malley KJ, Eisermann K, Pascal LE, Parwani AV, Majima T, Graham L, Hrebinko K, Acquafondata M, Stewart NA, Nelson JB, Yoshimura N, Wang Z. Proteomic analysis of patient tissue reveals PSA protein in the stroma of benign prostatic hyperplasia. Prostate. 2014 Jun;74(8):892-900. PubMed PMID: 24711254; PubMed Central PMCID: PMC4076791.

4. Liu J, Pascal LE, Isharwal S, Metzger D, Ramos Garcia R, Pilch J, Kasper S, Williams K, Basse PH, Nelson JB, Chambon P, Wang Z. Regenerated luminal epithelial cells are derived from preexisting luminal epithelial cells in adult mouse prostate. Mol Endocrinol. 2011 Nov;25(11):1849-57. PubMed PMID: 21940754; PubMed Central PMCID: PMC3198961

B. Positions and Honors

Positions and Employment

1988 - 1988 Laboratory Technician, University of South Florida, Department of Organic Chemistry, Tampa, FL

1989 - 1991  Chemist, Universal Waste & Transit, Tampa, FL

1992 - 1993 Environmental Intern, EcoTek, Inc., Tampa, FL

1993 - 1996 Project Chemist and Operations Supervisor, Nuclear Fuel Services, Radiation Protection Systems, Morris, IL

1996 - 1999 Environmental Engineer, Allitant Techsystems, Inc, Wilmington, IL

1999 - 2000 Environmental Scientist, Plexus Scientific, Chicago, IL

1999 - 2003 NIOSH Trainee, Graduate Student, University of Illinois at Chicago, School of Public Health, Chicago, IL

2004 - 2008 Post-doctoral Fellow, University of Washington, Department of Urology, Institute for Systems Biology, Seattle, WA

2008 - 2011 Post-doctoral Fellow, University of Pittsburgh, Department of Urology, Pittsburgh, PA

2011 - 2021 Research Assistant Professor, University of Pittsburgh School of Medicine, Department of Urology, Pittsburgh, PA

2021-           Research Assistant Professor, University of Pittsburgh School of Medicine, Department of Pharmacology and Chemical Biology, Pittsburgh, PA

Other Experience and Professional Memberships

2009 - Member, American Urological Society

2009 - Member, Society for Basic Urologic Research

2010 - Member, American Association for Cancer Research

Honors

2008 Travel Award, Society for Basic Urologic Research

2010 Travel Award, Great Lakes Nuclear Receptor Meeting

2010 Best of Posters Award, American Urological Association Foundation

2011 Travel Award, Society for Basic Urologic Research

2011 Travel Award, American Urological Association Foundation

2019  Best of Posters Award, American Urological Association Foundation

2019  Best of Posters Award, CAIRIBU, NIDDK

C. Contribution to Science

1. Determining the molecular mechanisms leading to benign prostatic hyperplasia (BPH).
   1. Wang K, Pascal LE, Li F, Chen W, Dhir R, Balasubramani GK, DeFranco DB, Yoshimura N, He D, Wang Z. Tight junction protein claudin-1 is downregulated by TGF-β1 via MEK signaling in benign prostatic epithelial cells. Prostate. 2020 Oct;80(14):1203-1215. PubMed Central PMCID: PMC7710618.
   2. Chen W, Pascal LE, Wang K, Dhir R, Sims AM, Campbell R, Gasper G, DeFranco DB, Yoshimura N, Wang Z. Differential impact of paired patient-derived BPH and normal adjacent stromal cells on benign prostatic epithelial cell growth in 3D culture. Prostate. 2020 Oct;80(14):1177-1187. PubMed Central PMCID: PMC7710585.
   3. Li F, Pascal LE, Wang K, Zhou Y, Balasubramani GK, O'Malley KJ, Dhir R, He K, Stolz D, DeFranco DB, Yoshimura N, Nelson JB, Chong T, Guo P, He D, Wang Z. Transforming growth factor beta 1 impairs benign prostatic luminal epithelial cell monolayer barrier function. Am J Clin Exp Urol. 2020;8(1):9-17. PubMed Central PMCID: PMC7076294.
   4. O'Malley KJ, Eisermann K, Pascal LE, Parwani AV, Majima T, Graham L, Hrebinko K, Acquafondata M, Stewart NA, Nelson JB, Yoshimura N, Wang Z. Proteomic analysis of patient tissue reveals PSA protein in the stroma of benign prostatic hyperplasia. Prostate. 2014 Jun;74(8):892-900. PubMed Central PMCID: PMC4076791.
2. Elucidation of the lineage relationship of the prostatic cell types, particularly epithelial cells in the adult prostate.
   1. Pascal LE, Rigatti LH, Ai J, Zhang A, Zhou J, Nelson JB, Wang Z. EAF2 loss induces prostatic intraepithelial neoplasia from luminal epithelial cells in mice. Am J Clin Exp Urol. 2020;8(1):18-27. PubMed Central PMCID: PMC7076293.
   2. Liu J, Pascal LE, Isharwal S, Metzger D, Ramos Garcia R, Pilch J, Kasper S, Williams K, Basse PH, Nelson JB, Chambon P, Wang Z. Regenerated luminal epithelial cells are derived from preexisting luminal epithelial cells in adult mouse prostate. Mol Endocrinol. 2011 Nov;25(11):1849-57. PubMed Central PMCID: PMC3198961.
   3. Pascal LE, Vêncio RZ, Vessella RL, Ware CB, Vêncio EF, Denyer G, Liu AY. Lineage relationship of prostate cancer cell types based on gene expression. BMC Med Genomics. 2011 May 23;4:46. PubMed Central PMCID: PMC3113924.
3. Stromal epithelial signaling in the development and progression of prostate cancer.
   1. Pascal LE, Ai J, Masoodi KZ, Wang Y, Wang D, Eisermann K, Rigatti LH, O'Malley KJ, Ma HM, Wang X, Dar JA, Parwani AV, Simons BW, Ittman MM, Li L, Davies BJ, Wang Z. Development of a reactive stroma associated with prostatic intraepithelial neoplasia in EAF2 deficient mice. PLoS One. 2013;8(11):e79542. PubMed Central PMCID: PMC3832612.
   2. Vêncio EF, Pascal LE, Page LS, Denyer G, Wang AJ, Ruohola-Baker H, Zhang S, Wang K, Galas DJ, Liu AY. Embryonal carcinoma cell induction of miRNA and mRNA changes in co-cultured prostate stromal fibromuscular cells. J Cell Physiol. 2011 Jun;226(6):1479-88. PubMed Central PMCID: PMC3968429.
   3. Pascal LE, Ai J, Vêncio RZ, Vêncio EF, Zhou Y, Page LS, True LD, Wang Z, Liu AY. Differential Inductive Signaling of CD90 Prostate Cancer-Associated Fibroblasts Compared to Normal Tissue Stromal Mesenchyme Cells. Cancer Microenviron. 2011 Jan 7;4(1):51-9. PubMed Central PMCID: PMC3047627.
   4. Pascal LE, Goo YA, Vêncio RZ, Page LS, Chambers AA, Liebeskind ES, Takayama TK, True LD, Liu AY. Gene expression down-regulation in CD90+ prostate tumor-associated stromal cells involves potential organ-specific genes. BMC Cancer. 2009 Sep 8;9:317. PubMed Central PMCID: PMC2745432.
4. Role of ELL-associated Factor 2 (EAF2) in prostate cancer development and progression.
   1. Zang Y, Pascal LE, Zhou Y, Qiu X, Wei L, Ai J, Nelson JB, Zhong M, Xue B, Wang S, Yang D, Lan L, Shan Y, Wang Z. ELL2 regulates DNA non-homologous end joining (NHEJ) repair in prostate cancer cells. Cancer Lett. 2018 Feb 28;415:198-207. PubMed Central PMCID: PMC5761340.
   2. Pascal LE, Masoodi KZ, Liu J, Qiu X, Song Q, Wang Y, Zang Y, Yang T, Wang Y, Rigatti LH, Chandran U, Colli LM, Vencio RZN, Lu Y, Zhang J, Wang Z. Conditional deletion of ELL2 induces murine prostate intraepithelial neoplasia. J Endocrinol. 2017 Nov;235(2):123-136. PubMed Central PMCID: PMC5679084.
   3. Ai J, Pascal LE, Wei L, Zang Y, Zhou Y, Yu X, Gong Y, Nakajima S, Nelson JB, Levine AS, Lan L, Wang Z. EAF2 regulates DNA repair through Ku70/Ku80 in the prostate. Oncogene. 2017 Apr;36(15):2054-2065. PubMed Central PMCID: PMC5386836.
   4. Pascal LE, Ai J, Masoodi KZ, Wang Y, Wang D, Eisermann K, Rigatti LH, O'Malley KJ, Ma HM, Wang X, Dar JA, Parwani AV, Simons BW, Ittman MM, Li L, Davies BJ, Wang Z. Development of a reactive stroma associated with prostatic intraepithelial neoplasia in EAF2 deficient mice. PLoS One. 2013;8(11):e79542. PubMed Central PMCID: PMC3832612.
5. Determine the potential for enhanced survival of androgen-sensitive prostate tumors treated with intermittent androgen deprivation therapy (IADT).
   1. Yang Z, Wang D, Johnson JK, Pascal LE, Takubo K, Avula R, Chakka AB, Zhou J, Chen W, Zhong M, Song Q, Ding H, Wu Z, Chandran UR, Maskrey TS, Nelson JB, Wipf P, Wang Z. A Novel Small Molecule Targets Androgen Receptor and Its Splice Variants in Castration-Resistant Prostate Cancer. Mol Cancer Ther. 2020 Jan;19(1):75-88. PubMed Central PMCID: PMC6946849.
   2. Jing Y, Nguyen MM, Wang D, Pascal LE, Guo W, Xu Y, Ai J, Deng FM, Masoodi KZ, Yu X, Zhang J, Nelson JB, Xia S, Wang Z. DHX15 promotes prostate cancer progression by stimulating Siah2-mediated ubiquitination of androgen receptor. Oncogene. 2018 Feb 1;37(5):638-650. PubMed Central PMCID: PMC5794523.
   3. Masoodi KZ, Eisermann K, Yang Z, Dar JA, Pascal LE, Nguyen M, O'Malley K, Parrinello E, Feturi FG, Kenefake AN, Nelson JB, Johnston PA, Wipf P, Wang Z. Inhibition of Androgen Receptor Function and Level in Castration-Resistant Prostate Cancer Cells by 2-[(isoxazol-4-ylmethyl)thio]-1-(4-phenylpiperazin-1-yl)ethanone. Endocrinology. 2017 Oct 1;158(10):3152-3161. PubMed Central PMCID: PMC5659684.

Masoodi KZ, Xu Y, Dar JA, Eisermann K, Pascal LE, Parrinello E, Ai J, Johnston PA, Nelson JB, Wipf P, Wang Z. Inhibition of Androgen Receptor Nuclear Localization and Castration-Resistant Prostate Tumor Growth by Pyrroloimidazole-based Small Molecules. Mol Cancer Ther. 2017 Oct;16(10):2120-2129. PubMed Central PMCID: PMC5628124.

Complete List of Published Work in My Bibliography