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Kristine M

Senior Scientist

Profile

-Scientist with 15 years experience in molecular biology, cell biology, and pathology in the cancer research and cardiac research fields with 23 peer-reviewed publications and over 1200 citations on Google Scholar

-Experimental expertise in oncology, cardiac biology, transcription factors, epigenetics, 3D organoid cell culture, in vivo disease modeling, single cell sequencing, targeted protein degradation, and drug discovery

-Sustained service at the institute, local, and national levels in biomedical workforce training initiatives, K-12 science education, and science policy

Key Skills & Competencies

I have fifteen years experience in the research laboratory setting, seven of those are post-degree work and nearly three of those are in the pharmaceutical industry. I have worked in both cardiovascular disease and oncology, with specific work in molecular endocrinology, transcription factor regulation, and epigenetics. My experimental expertise spans from general molecular biology techniques to single cell RNA sequencing/RNA sequencing, also including 3D cell culture and organoids, assay development, early drug discovery, and translational research.

Professional Experience

Arvinas, Inc, New Haven, CT, 2.75 years
Senior Research Scientist, Oncology
Project Leadership
•Biology Lead for 5 unique projects, with final decisions made on 4 projects in only 2.5 years.
•Designed experimental timelines to achieve early discovery project decisions with leadership as quickly as possible.
•Combined and analyzed data for entire research group to streamline final analysis and project messaging.
•Presented with Chemistry Lead to multiple stakeholders, including our project group, the entire oncology staff, and Arvinas leadership committee as part of discovery governance.
•Designed, performed, and project-managed translational research to support early development team, informing patient selection, combination strategies, resistance mechanisms, and target validation for newly announced
BCL6 PROTAC® ARV-393, planned to begin Phase 1 clinical trials in 2024 for B cell lymphomas
•Member of working group identifying new oncology targets for Arvinas’ PROTAC® technology

Management Experience
•Managed 1 report directly and other reports in matrix as needed on a project-by-project basis.
•Conducted research daily at the bench alongside my reports and determined daily experimental goals.
•Held 1:1 meetings with my report 2x/week, totaling 2 hours/week.
•Trained in Situational Leadership® from Ashley Miles Consulting and participated in optional DEI training.

Laboratory Research
•Designed and carried out protein degradation assays to test individual PROTACs® using western blot.
•Assisted in design of high throughput protein degradation assays for PROTAC® screening using high content (HC).
•Planned with and supervised my report in performing CRISPR-based cell line development.
•Performed protein degradation assaying using dTAG-based technology with cell lines generated in-house.
•Devised and carried out cell-based ligand binding assays including thermal shift assays (TSA) and NanoBRET®.
•Identified markers and performed downstream target engagement assays using western blot, qRT-PCR, and ELISA.
•Designed and performed 96-well functional cell death assays using IncuCyte®, CellTiter-Glo®, and Caspase-Glo® 3/7 to test efficacy and efficiency of tool PROTACs® against cancer in vitro.

Roswell Park Cancer Institute, Buffalo, NY
Research Affiliate-Postdoctoral
Laboratory of David W Goodrich, 5 years
Laboratory Research
•Researched how certain genetic and epigenetic changes contribute to treatment resistance and lineage plasticity in prostate cancer by utilizing three major techniques: genetically engineered mouse models (GEMMs), 3D organoid culturing, and single-cell RNA sequencing.
•Developed new GEMM of prostate cancer lacking a key gene regulator (Ezh2): characterized disease in 250+ mice using necropsy, immunohistochemistry (IHC), RNA sequencing, and single cell RNA sequencing.
•See Wadosky et al. Cancer Res. 2023. 83 (11_Supplement): Abstract nr PR008. Manuscript in preparation.
•Maintained my own GEMM breeding colonies, genotyped 1300+ mice, and recorded data in Softmouse Software.
•Tested anti-tumor efficacy of 2 EZH2 inhibitors in 2 GEMMs of prostate cancer using multiple treatment schedules, collaborating with Constellation Pharmaceuticals (now MorphoSys).
•Developed 20+ mouse prostate tumor 3D organoid lines and attempted to establish human prostate 3D organoid lines from 10+ fresh surgical specimens from transurethral resection of the prostate (TURP).
•See Wadosky* et al. J Vis Exp. 2019:(148):10.3791/5910; *corresponding author.
•Applied 3D cell culture techniques to develop novel media to maintain neuroendocrine features of original tumors.
•Trained with collaborator Charles Sawyers on single-cell RNA sequencing technology.
•Established protocols for Goodrich lab and trained other researchers to do the technique. Became an expert on single cell RNA-sequencing from prostate GEMMs, collaborating on 3 studies including 1 published in Science.
oSee Chan et al. Science. 2022;377(6611):1180-1191., Zaidi et al. Proc Natl Acad Sci USA. 2024;121(28)., Ku et al. J Clin Invest. 2024 Jul 18. Online ahead of print.

Management Experience
•Supervised 3 rotation students, 2 PhD candidates, 1 medical resident, and 2 technicians.

Roswell Park Cancer Institute, Buffalo, NY
Research Affiliate- Postdoctoral
Laboratory of Shahriar Koochekpour, 1.5 years
•Identified mechanism of action of riluzole against androgen receptor using human prostate cancer cell lines.
•Completed project in only 1.5 years, while also writing 3 review articles on advanced prostate cancer.

Community Experience

Junior Achievement (JA) of Southwest New England
Volunteer and Event Organizer, 2 years
•Volunteered to teach “JA in a Day” curriculum to 4th grade students during Arvinas’ Impact Day.
•Established and managed collaboration between JA, CT chapter of Women in Biology (WIB), and Arvinas, Inc. for “Careers in STEM” event. Recruited 4 Arvinas, Inc volunteers to implement hands-on experiments I designed to teach high school students about Arvinas’ PROTAC® technology.
•Participated in JA-sponsored career day at Guilford High School.

Science Fair Planning Committee, Willie Hutch Jones Educational and Sports Program
Chair of Planning Committee, 4 years
•Directed meetings for six-person committee, managed registrations for 25+ participants/year in the City of Buffalo.
•Promoted fair by giving interviews at local radio and TV news stations, acting as a spokesperson.
•Oversaw operations on the day of the event, resolved unforeseen problems, and certified final scores and winners.

Research and Science Policy Committee, American Society for Investigative Pathology
Junior Member, 4 years
•Discussed public affairs related to biomedical research including policies on human and animal subjects, government funding, workforce initiatives for trainees, patent law, biorepositories, and HIPPA and CLIA laws.

Education

University of North Carolina at Chapel Hill
PhD, Pathology

University of Rochester
BS, Molecular Genetics

University of Rochester
BA, English Literature, concentration in Theater

Other Experience/Awards/Publications

-Completed research experience for undergraduates (REU) at Harvard University, Center for Systems Biology
-National Science Foundation, Graduate Research Fellowship Award, Honorable Mention
-American Heart Association, Graduate Research Predoctoral Grant
-American Physiological Society, Endocrinology and Metabolism Section, Recognition Award for Meritorious Research by a Young Investigator
-American Physiological Society, Endocrinology and Metabolism Section, Research Recognition Award
-American Society for Investigative Pathology, Abraham D. Sobel ASIP Educational Fund Scholar
-American Society for Investigative Pathology, Trainee Travel Award
-Society for Endocrinology, Journal of Molecular Endocrinology Award for publication Wadosky KM et al. J Mol Endocrinol. doi: 10.1530/JME-15-0283.
-Western New York STEM Hub Mentorship Award, for inspiring Women and Girls as a STEM mentor
-Thermo Fisher Gibco Cell Culture Heroes Award
-American Society for Investigative Pathology, Young Scientist Leadership Award

PUBLICATIONS (reverse chronological order):
A. Original Manuscripts
1. Ku SY, Wang Y, Garcia MM, Yamada Y, Mizuno K, Long MD, Rosario S, Chinnam M, Al Assaad M, Puca L, Kim MJ, Bakht MK, Venkadakrishnan VB, Robinson BD, Acosta AM, Wadosky KM, Mosquera JM, Goodrich DW, Beltran H. Notch signaling suppresses neuroendocrine differentiation and alters the immune microenvironment in advanced prostate cancer. J Clin Invest. 2024 Jul 18; 134(17):e175217.

2. Zaidi S, Park J, Chan JM, Roudier MP, Zhao JL, Gopalan A, Wadosky KM, Patel RA, Sayar E, Karthaus WR, Kates DH, Chaudary O, Xu T, Masilionis I, Mazutis L, Chaligné R, Obradovic A, Linkov I, Barlas A, Jungbluth AA, Rekhtman N, Silber J, Manova-Todorova K, Watson PA, True LD, Morrissey C, Scher HI, Rathkopf DE, Morris MJ, Goodrich DW, Choi J, Nelson PS, Haffner MC, Sawyers CL. Single-cell analysis of treatment-resistant prostate cancer: Implications of cell state changes for cell surface antigen-targeted therapies. Proc Natl Acad Sci U S A. 2024 Jul 9;121(28):e2322203121.

3. Chan JM, Zaidi S, Love JR, Zhao JL, Setty M, Wadosky KM, Gopalan A, Choo ZN, Persad S, Choi J, LaClair J, Lawrence KE, Chaudhary O, Xu T, Masilionis I, Linkov I, Wang S, Lee C, Barlas A, Morris MJ, Mazutis L, Chaligne R, Chen Y, Goodrich DW, Karthaus WR, Pe’er D, Sawyers CL. Lineage plasticity in prostate cancer depends on JAK/STAT inflammatory signaling. Science. 2022 Sep 9;377(6611):1180-1191.

4. Pearson JD, Huang K, Pacal M, McCurdy SR, Lu S, Aubry A, Yu T, Wadosky KM, Zhang L, Want T, Gregorieff A, Ahmad M, Dimaras H, Langille E, Cloe SPC, Monnier PP, Lok BH, Tsao MS, Akeno N, Schramek D, Wikenheiser-Brokamp KA, Knudsen ES, Witkiewicz AK, Wrana JL, Goodrich DW, Bremner R. Binary pan-cancer classes with distinct vulnerabilities defined by pro- or anti-cancer YAP/TEAD activity. Cancer Cell. 2021 Aug 9;39(8):115-1134.e12.

5. Park SH, Fong KW, Kim J, Wang F, Lu X, Lee Y, Bres LT, Wadosky KM, Guo C, Abdulkadir SA, Crispino JD, Fang D, Ntziachristos P, Liu X, Wan Y, Goodrich DW, Zhao JC, Yu J. Posttranslational regulation of FOXA1 by Polycomb and BUB3/USP7 deubiquitin complex in prostate cancer. Sci Adv. 2021 Apr 7;7(15):eabe2261.

6. Burkhart DL, Morel KL, Wadosky KM, Labbe DP, Galbo P, Dalimov Z, Xu B, Loda M, Leigh Ellis L. Evidence that Ezh2 Deregulation is an Actionable Therapeutic Target for Prevention of Prostate Cancer. Cancer Prev Res. 2020 Dec;13(12): 979-988.

7. Sobel ME, Dreyfus JC, McKillip KD, Kolarcik C, Muller WA, Scott MJ, Siegal GP, Wadosky KM, O’Leary TJ. Return of Individual Research Results: A Guide for Biomedical Researchers Utilizing Human Biospecimens. Am J Pathol. 2020 May; 190(5): 918-933.

8. Wadosky KM*, Wang Y, Zhang X, Goodrich DW. (2019) Generation of Tumor Organoids from Genetically Engineered Mouse Models of Prostate Cancer. J Vis Exp. 2019 Jun 13;(148). *Corresponding author

9. Wadosky KM, Shourideh M, Goodrich DW, Koochekpour S. (2019) Riluzole induces AR degradation via endoplasmic reticulum stress in androgen-dependent and castration-resistant prostate cancer cells. Prostate. 2019 Feb;79(2):140-150.

10. Korshunov V, Mickelsen D, Fowell D, Dugbartey G, Wadosky KM, Ko K, Wood R, Batchu S, Yang X, Zhao Y. (2018) Innate immune cells are regulated by Axl in hypertensive kidney. Am J Pathol. 2018 Aug; 188(8):1794-1806.

11. Labbé DP, Sweeney CJ, Brown M, Galbo P, Rosario S, Wadosky KM, Ku S, Sjöström M, Alshalalfa M, Erho N, Davicioni E, Karnes RJ, Shaeffer EM, Jenkins RB, Den RB, Ross AE, Bowden M, Huang Y, Gray KP, Feng FY, Spratt DE, Goodrich DW, Eng KH, Ellis L. (2017) TOP2A and EZH2 provide early detection of an aggressive prostate cancer subgroup. Clin Cancer Res. 2017 Nov 15; 23(22):7072-7083. doi: 10.1158/1078-0432.CCR-17-0413.

12. Wadosky KM, Ellis L, Goodrich DW. (2017) Evasion of Targeted Cancer Therapy through Stem Cell-Like Reprogramming. Mol Cell Oncol. 2017 Feb 16;4(2):e1291397. doi: 10.1080/23723556.2017.1291397.

13. Wadosky KM, Koochekpour S. (2017) Androgen receptor splice variants and prostate cancer: From bench to bedside. Oncotarget. 2017 Mar 14;8(11):18550-18576. doi: 10.18632/oncotarget.14537.

14. Wadosky KM, Koochekpour, S. (2016) Molecular mechanisms underlying resistance to androgen deprivation therapy in prostate cancer. Oncotarget. 2016 Sep 27;7(39):64447-64470. doi: 10.18632/oncotarget.10901.
15. Batchu SN, Hughson A, Wadosky KM, Morrell CN, Fowell DJ, Korshunov VA. (2016) The role of Axl in T lymphocyte survival in salt-dependent hypertension. Arterioscler Thromb Vasc Biol. 2016 Aug;36(8):1638-46. doi: 10.1161/ATVBAHA.116.307848.
16. Wadosky KM, Berthiaume J, Tang W, Zungu M, Portman MA, Gerdes M, Willis MS. (2016) MuRF1 mono-ubiquitinates TRα to inhibit T3 induced cardiac hypertrophy in vivo. J Mol Endocrinol. 2016 Apr;56(3):273-90. doi: 10.1530/JME-15-0283.
Winner of the Society of Endocrinology Journal Award, 2017.

17. Wadosky KM, Koochekpour, S. (2016) Therapeutic Rationales, Progresses, Failures, and Future Directions for Advanced Prostate Cancer. Int J Biol Sci. 12(4): 409-426. doi: 10.7150/ijbs.14090.

18. Wadosky KM, Rodriguez JE, Hite RL, Min JN, Walton BL, Willis MS. (2014) Muscle RING finger-1 attenuates IGF-1-dependent cardiomyocyte hypertrophy by inhibiting JNK signaling. Am J Physiol Endocrinol Metab. 2014 Apr; 306(7):E723-39. doi: 10.1152/ajpendo.00326.2013.

19. Willis MS, Wadosky KM, Rodriguez JE, Schisler JC, Lockyer P, Hillard EG, Glass DJ, Patterson C. (2014) Muscle ring finger 1 and muscle ring finger 2 are necessary but functionally redundant during developmental cardiac growth and regulate E2F1-mediated gene expression in vivo. Cell Biochem Funct. 2014 Jan; 32(1):39-50. doi: 10.1002/cbf.2969.

20. Cotton SW, Kornegay JN, Bogan DJ, Wadosky KM, Patterson C, Willis MS. (2013) Genetic myostatin decrease in the golden retriever muscular dystrophy model does not significantly affect the ubiquitin proteasome system despite enhancing the severity of disease. Am. J. Transl. Res. 2013 Dec 1; 6(1):43-53.

21. Willis MS, Min JN, Wang S, McDonouch H, Lockyer P, Wadosky KM, Patterson C. (2013) Carboxyl terminus of Hsp70-interacting protein (CHIP) is required to modulate cardiac hypertrophy and attenuate autophagy during exercise. Cell Biochem Funct. 2013 Dec; 31 (8):724-35. doi: 10.1002/cbf.2962.

22. Wadosky KM, Willis, MS. (2012) The story so far: post-translational regulation of peroxisome proliferator-activated receptors (PPARs) by ubiquitination and SUMOylation. Am J Physiol Heart Circ Physiol. 302(3): H515-26. doi: 10.1152/ajpheart.00703.2011.

23. Wadosky KM, Li L, Rodriguez JE, Min J, Bogan D, Gonzalez J, Patterson C, Kornegay JN, Willis MS. (2011) Regulation of the calpain and ubiquitin proteasome systems in a canine model of muscular dystrophy. Muscle Nerve. 44(4):553-62. doi: 10.1002/mus.22125.

B. Award Lectures
1. Wadosky KM. Characterization of Ezh2-Deficient genetically engineered mouse models of neuroendocrine-differentiated prostate cancer. American Society for Investigative Pathology (ASIP) Young Scientist Leadership Award Lecture. ASIP Annual Meeting at Experimental Biology 2022.

2. Wadosky KM. Using 3D organoid culture to assess disease aggressiveness in genetically engineered mouse models of prostate cancer. Thermo Fisher Gibco Cell Culture Heroes Award Lecture. American Society for Cell Biology 2018. Lecture can be streamed here: https://players.brightcove.net/3663210762001/hmATFP49Og_default/index.html?videoId=5989365940001&_=1722038400095

C. Abstract Oral Presentations
1. Wadosky KM, Ku SY, Wang Y, Zhang X, Wang J, Wang J, Beltran H, Goodrich DW. Molecular determinants of prostate cancer lineage plasticity. Proceedings of the AACR Special Conference: Advances in Prostate Cancer Research. Cancer Res 2023;83(11 Suppl):Abstract nr PR008. Presentation given by DW Goodrich.

2. Wadosky KM, Wang Y, Goodrich DW. Ezh2 loss is a haplo-insufficient mediator of cell lineage in prostate cancer and has divergent effect on androgen receptor expression. FASEB J. 2020. 34 (S1). Supplement: Experimental Biology 2020 Meeting Abstracts.
3. Wadosky KM, Wang Y, Ellis L, Goodrich DW. Ezh2 is a dose-dependent mediator of prostate cancer aggressiveness and lineage transformation. Cancer Res. 2018. 78 (13 Supplement), 3016-3016.
4. Wadosky KM, Batchu SN, Hughson A, Donlon K, Morrell CN, Fowell DJ, Korshunov VA. (2014) Axl expression by CD4+ T lymphocytes promotes salt-dependent hypertension. Hypertension. 2014; 64: A001.

5. Wadosky KM, Hite RL, Willis MS. (2013) Muscle RING Finger-1 (MuRF1) inhibits insulin-like growth factor-1 (IGF-1)-dependent cardiomyocyte hypertrophy by reducing Akt nuclear activity. FASEB J April 9, 2013 27 (386.4).

6. Wadosky KM, Zungu M, Portman M, Gerdes AM, Willis MS. (2012) Muscle RING finger-1 (MuRF1) inhibits thyroid receptor (alpha) transcriptional activity and thyroid-hormone dependent cardiac hypertrophy. FASEB J, 2012: 26 (137.6).

D. Abstract Poster Presentations
1. Zhao JL, Zaidi S, Chan J, Wadosky K, Karthaus W, Choi D, Rivera AA, Gopalan A, Rathkopf DE, Carver BS, Abida W, Scher H, Chen Y, Goodrich D, Pe’er D, Sawyers CL. Identification of the cells of origin and tumor heterogeneity in neuroendocrine prostate cancer (NEPC) by single-cell analysis. (2020) AACR Virtual Special Conference: Tumor Heterogeneity: From Single Cells to Clinical Impact.

2. Gaddy J, Goodrich DW, Chatta G, Wadosky KM. Enzalutamide and decitabine in combination inhibits growth of castration resistant prostate cancer cells with a greater response than enzalutamide alone. (2018) 30th EORTC-NCI-AACR Research Symposium. Eur J Can. Nov. 1 2018. 103, E119-E119.

3. Wadosky KM, Hite RL, Willis MS. (2013) Muscle RING finger-1 (MuRF1) inhibits thyroid hormone-dependent cardiomyocyte growth in vitro and in vivo. FASEB J April 9, 2013 27 (936.5).

4. Willis MS, Wadosky KM, Patterson WC. (2013) Muscle Ring Finger 1 (MuRF1) and MuRF2 Regulate Gene Expression Mediated by the E2F Transcription Factors and are Necessary but Functionally Redundant During Developmental Cardiac Growth In Vivo. FASEB J April 9, 2013. 27, (1085.10).

5. Willis MS, Min JN, Wang S, Wadosky KM, Patterson WC. (2013) Carboxyl terminus of Hsp70-interacting protein (CHIP) is required to modulate cardiac hypertrophy and attenuate autophagy during exercise. FASEB J April 9, 2013 27. (711.7)

6. Cotten SW, Wadosky KM, Bogan D, Kornegay JN, Willis MS. (2012) Regulation of the calpain and ubiquitin proteasome system in a canine model of muscular dystrophy with myostatin inhibition. FASEB J, 2012: 26 (478.3).

7. Wadosky KM, Rodriguez JE, Min J, McDonough H, Lockyer P, Walton B, Patterson WC, Willis MS. (2011) The ubiquitin ligases CHIP and MuRF1 inhibit physiological cardiac growth (hypertrophy) in response to exercise. Sigma Xi Annual Meeting and International Research Conference. 2011.

8. Wadosky KM, Rodriguez JE, Li L, Bogan D, Kornegay JN, Willis MS. (2011) Regulation of the ubiquitin proteasome and calpain systems in a dog model of duchenne muscular dystrophy. FASEB J, 2011: 25 (1000.8).

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