Profile

Mary Regina Saunders, PhD 

Achiever, Ideation, Futuristic, Learner, Input- Strength Finders

Summary:

• Experience in leading highly dynamic teams and engaging in effective collaborations across diverse disciplines to ensure data-driven and robust safety assessment of potential therapeutics
• Design and manage toxicology experiments, interpret and translate results, contribute to drug discovery and development, lead toxicology innovation, and identify and solve problems
• Experience as Study Director conducting and monitoring toxicology studies under Good Laboratory Practice regulations, supporting issue resolution, operating in a highly collaborative environment interacting with multiple internal and external stakeholders, and contributing to high quality and timely deliverables
• Experience with diverse therapeutic modalities, including small molecules, peptides, and monoclonal antibodies
• Excellent verbal and written skills; strong interpersonal, organizational, and team-oriented skills

Predictive, Investigative, and Translational Toxicology (PITT), Nonclinical Sciences (NCS)
March 2020 – Present

Responsibilities:

• Drives experimental strategies regarding hematology and immune system-mediated toxicities associated with small and large molecules, cellular, gene, and RNA therapies
• Deep comprehension of target biology to drive the design and execution of custom functional hematopoietic and immune cell-based assays to understand and predict immune mechanistic safety liabilities
• Independently designs, conducts and executes experiments to evaluate the effects of immunomodulatory compounds using various in vivo and model systems in vitro following Data Integrity standards, and writing reports for regulatory submission
• Interacts with CROs at multiple levels, including transferring methods developed at Janssen, monitoring CRO validations, and monitoring immune endpoints during both GLP and non-GLP studies
• Investigates and develops novel experimental methods/technologies, contributes to improvement of existing methods, and develops new in vitro/in vivo models to enhance our understanding of potential hematotoxicity and immunotoxicology risk and translatability to humans in the clinic
• Participates in communication of information and data presentation in oral and written format both in-house and at appropriate external forums
• Provides mentorship for scientists and associates in the laboratory

Project Highlights:

Lead cross-disciplinary efforts as HIT Study Director/Project Lead to investigate potential hematological and immunological related liabilities through better technologies and novel techniques for the following projects:

• P2X7R- Prepared Immune TLA (target liability assessment)/White paper, and planned in vivo model development through collaboration with external Immunotoxicology CRO, Burlington Research Technologies
• DHODHi- Used HALO platform and CFU to assess proliferation of primitive hematopoietic cells in 3 lineages across 4 species with specialty CRO, Hemogenix, with lead molecule
• GPRC5D/BCMA/CD3- designed and developed protocols to determine cyno cross-reactivity of Janssen GPRC5D and BCMA antibodies at Champions Antibodies will be used within a flow cytometry panel to immunophenotype and monitor plasma cells on non-human primate studies
• Assumed lead role to develop T cell activation assays (using the methods of Romer and Stebbings), for WERTH due diligence in order to evaluate potential cytokine release syndrome (CRS) liability with this molecule relative to other T-cell agonists
• HLA-G/SMARCA2/ Ponesimod- Completed TLA for SMARCA2 to evaluate potential endothelial Wrote endothelial cell guideline and planned for possible study placement of endothelial cell progenitor assays at Stem Cell Technologies (SCT) for the HLA-G program.
• PIWG/PSTC/HESI- Contributed to miRNA biomarker development for exocrine and endocrine pancreas Provided data to the consortium to support the FDA approval of a miRNA biomarker.  Evaluated 3 CROs, Abcam, Reveal and ACD, to validate in vitro and in vivo pancreatic toxicity findings using serum, tissues, cell cultures and FFPE blocks
• Ibrutinib- Utilized In vivo, in vitro, and in silico analysis to investigate RNA-seq and IHC gene and protein expression to support risk assessment for a cardiac toxicity/liability
• Contributed to Platelet activation assay method development- a flow cytometry-based assay using NHP and human platelets that will support multiple programs
• PRMT5- Provided intellectual input for hematotoxicity assessment for an oncology indication
• Developed imaging laboratory for vital 3D holotomography microscopy and advanced fluorescent microscopy to evaluate real-time effects of drugs and cellular activity, cellular metabolism, cell cycle analysis, cell-cell interactions, and cell behavior in in vivo-like systems

Internal Support:

• Supported risk mitigation strategies for a diverse global portfolio by performing appropriate investigative studies, utilizing Body Map and data related resources
• Supported the recruitment, onboarding and acclimation of PITT scientists
• Supported an ethical and complaint work environment adherent to standards of quality and safety; DDI compliance
• Served as a member of the NCS Playbook Team, Scientist Mentoring and Diversity Program (SMDP); DPDS Mentoring Program; PITT/NCS D&I (Diversity and Inclusion) Core Team, Women’s Leadership Initiative; J&J Masks for COVID-19 Firstline workers and children; and HIT Scientists Support Group
• Provided lab space, building support, and equipment management to team members of HIT during construction phase of new laboratory site

External Influence Activities:

• Invited Guest lecturer at California State University Clinical Laboratory Sciences Program (Hematology, Clinical Pathology), Public Health Administration Program
• Invited Guest lecturer at California State University Northridge, Health Administration Program – IPE (Interprofessional Education) Collaboration and Leadership Meeting
• Provided project support for University of Massachusetts Public Health graduate students

Continuing Education:

• Software: Tableau Creator, 2020; Tableau Explorer, 2020; Broad Institute DepMap, 2020; cBioPortal for Cancer Genomics, 2020; COSMIC Catalogue of Somatic Mutations, 2020; ArrayStudio –Omic Software, 2020; STEVE, Carl Zeiss Imaging
• LinkedIn Learning (2020): Discovering Your Strengths, Well-Being and Productivity, Balancing Work and Life, Time Management: Working from Home, Leading at a Distance, Professional Networking
• Society of Toxicologic Pathology, Davis-Thompson DVM Foundation: Toxicologic Pathology
• American College of Toxicology: Toxicology for Pharmaceutical and Regulatory Scientists, Advanced Comprehensive Toxicology

Preclinical Development and Safety (PDS), Discovery Sciences
January 2017 – March 2020

Responsibilities:

• Independently hypothesize, design, and execute in vivo and in vitro study projects and analyze results
• Design and conduct in vivo discovery, mechanistic and investigative toxicology studies in rats and mice, including but not limited to clinical observations, dosing, bleeding, euthanasia, tissue dissection, and data collections
• Execute hands-on research utilizing state-of-the-art toxicology, cell and molecular biology, and biochemistry methods, including RNA/DNA/protein extractions, RT-qPCR, western blot analysis, conventional ELISA, fluorescence immunoassays, in situ hybridization and immunohistochemistry staining
• Demonstrate wide-ranging expertise in safety biomarker measurement; molecular pathology; cell culturing techniques to utilize primary, stem, and cancer cell lines; and cell/tissue imaging methods, confocal and applied tomographic microscopy
• Actualize broad scientific knowledge of immunology, neuroscience, animal models of disease, and predictive assay development to support nonclinical safety assessments
• Support pro-active risk assessment of potential target and chemotype-related toxicity issues
• Generate target assessments and actualize compound safety profiling strategies
• Engage in external collaborations with industry and academia to assess breakthrough platforms to de-risk compound safety liability issues within defined time frames
• Interpret data generated by other therapeutic areas (TAs) and CROs to generate a comprehensive toxicology assessment
• Apply research documentation and review skills including the research study calendar, study protocols, data tables, and quality control/assay validation results using Microsoft Word, PowerPoint and/or Excel, generation of statistical analysis (using GraphPad Prism and Janssen Quantitative Sciences/ Discovery Sciences Apps software), electronic laboratory notebook entries, and study reports to draw valid conclusions
• Serve as the primary collaborator for external investigative studies
• Draft and execute peer-reviewed manuscripts
• Attend and present breakthrough data at in-house research seminars, forums, and national conferences

Project Highlights:

Proactively evaluated the competitive landscape and participated in issue-resolution teams to generate hypotheses and deliver value added results throughout the drug discovery & development process:

• Led the validation process for implementing flow cytometry as an innovative platform for detecting microRNAs in biological fluids and tissues to predict drug-induced acinar atrophy
  • Validated data sets of pancreas-enriched microRNAs in serum and pancreas tissue
  • Cross-validated using RT-PCR
  • Collaborated with external partner to develop in situ hybridization method for localizing microRNAs in rat pancreas tissues
  • Demonstrated utility of novel platform to evaluate biomarkers in drug-induced toxicities
  • Supplement in vivo/ex vivo investigations to support biomarker identification and investigate toxicity studies to de-risk compound/project
• Optimized new experimental models and technologies to support internal projects
  • Developed primary and stem cell cultures to mimic specific organs (pancreas, brain, cardiovascular, skeletal muscle)
  • Evaluated the utility of biomarkers to enable early drug induced injury identification
• Acquired novel imaging technology to investigate cell behavior in in vivo-like systems

University of California, Davis
Ph.D. Comparative Pathology, June 2013
Designated Emphasis in Biotechnology,  Designated Emphasis in Translational Research

Thesis: Discovery of Novel Human Stem Cell and Cancer Glycans for Therapeutic Investigations

M.S. Clinical Sciences: Medical Technology

Basic and Clinical Medical Sciences, International Medical Education and Research Training

Specialized Ed.M. Risk and Prevention Public Health: Infectious Diseases

• State of California, Department of Health Services, Clinical Laboratory Scientist CLS (CA) License # MTA 40802 (File ID 44972)
• American Society for Clinical Pathology, Medical Technologist/ Medical Laboratory Scientist/ Medical Laboratory Scientist MT/MLS (ASCP) License # MT-221489

Postdoctoral Fellowship                                                                                                           Jan 2014 – Dec 2016

Indiana University School of Medicine, Department of Microbiology and Immunology  Ruth L. Kirschstein National Research Service Award Trainee for T32 HL007910

Basic Science Studies on Gene Therapy of Blood Diseases (PI: Hal Broxmeyer, Ph.D.) Laboratory of Louis M. Pelus, Ph.D.

• Identified autophagy as a mechanism of response of megakaryocytes in radiation and drug induced stress
• Validated young and aged murine models with known medical countermeasures against lethal radiation exposure for eventual licensure by the FDA
• Evaluated the delayed effect of acute radiation exposure (DEARE) in young and aged mice survivors of Hematopoietic Acute Radiation Syndrome (H-ARS)
• Adapted sorting and dissecting techniques to purify primary cultures and cell lines for use in expression system technologies

PhD Research Fellowship                                                                                                           June 2006 – Dec 2012

University of California, Davis

NIH Initiative for Maximizing Student Diversity (NIH-IMSD) Fellowship NIH-R25-GM56765, NIH Research Supplement to Promote Diversity in Health-Related Research NIH-U19-CA113298, Howard Hughes Medical Institute - Integrating Medicine into Basic Science (HHMI-IMSD) Fellowship Med into Grad Initiative 56005706 Laboratories of Kit S. Lam, MD, PhD and Suzanne Miyamoto, PhD

• Identified and optimized targeting agents for stem cells, hematological and solid tumor cells for therapeutic efficacy; developed novel combinatorial strategies for high throughput screening
• Translational research projects to identify relevant glycomic biomarkers of cancer and stem cells to assist with diagnosis, early detection, and monitoring of treatment for hematological and solid tumor cancers

Society of Toxicologic Pathology, American College of Toxicology,  Society of Toxicology, International Society of Experimental Hematology, American Society of Hematology, International Society for Stem Cell Research, American Association for Cancer Research, American Society for Clinical Pathology, Toastmasters International

• Saunders MR, Sahdeho S, Ma JY, Carreira V, Wang E, Glaab W, Snook S, McDuffie In vivo to in vitro detection of microRNAs as injury markers in models of acute pancreas toxicity. For submission to International Journal of Toxicology, 2021.
• Saunders MR, Behesti Zavareh R, Snook S, McDuffie Electrophysiological modeling of exocrine pancreas mimetics for toxicological investigations. For Submission to Toxicology In Vitro, 2021.
• Saunders MR and Pelus Pharmokinetic investigations of young and aged irradiated and PGE2 treated mice using LC-MS/MS. Submitted to Blood Cells, Molecules, and Disease, 2020, Resubmission in progress.
• Hua S*, Saunders M*, Dimapasoc LM, Jeong SH, Kim BJ, Kim S, So M, Lee KS, Kim JH, Lam KS, Lebrilla CB, An Differentiation of cancer cell origin and molecular subtype by plasma membrane N-glycan profiling. Journal of Proteome Research, 2014 Feb 7;13(2):961-8. doi: 10.1021/pr400987f. Epub 2014 Jan 8. PMID: 24303873 January 2014 (*Shared First Authorship)
• Yao W, Gaun M, Jia J, Lay YE, Dai W, Amugongo S, Liu R, Olivos D, Saunders M, Lam KS, Nolta J, Olvera D, Ritchie RO, Lane Bone loss induced by estrogen deficiency and aging by directed mesenchymal stem cells to bone. Stem Cells Stem Cells. 2013 Sep;31(9):2003-14. doi: 10.1002/stem.1461. Erratum in: Stem Cells. 2014 Feb;32(2):601. PMID: 23818248
• Kumaresan PR, Wang Y, Saunders M, Maeda Y, Liu R, Zhu M, Wang X, Lam (2011). Rapid discovery of death ligands with one-bead two-compound combinatorial library methods. ACS Combinatorial Science, 13(3): 259- 64. doi: 10.1021/co100069t. Epub 2011 Feb 8. PMID: 21302937 doi: 10.1021/co100069t. Epub 2011 Feb 8.
• Saunders MR, Ruhaak LR, Williams C, Olivos DJ, Stroble C, An HJ, Miyamoto S, Lebrilla CB, Lam Dasatinib regulation of N-glycans induces anticancer activity in hematological and solid tumor malignancies [abstract]. In: Proceedings of the Fifth AACR Conference on The Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2012 Oct 27-30; San Diego, CA. Philadelphia (PA): AACR; 2012. p

98. Abstract nr A41. Accepted to Cancer Epidemiology, Biomarkers & Prevention, February 2013

• Olivos DJ, Saunders, MR, Li Y, Al Awwad N, Lam Discovery of novel luteinizing hormone releasing hormone (LHRH) peptides as a nanotherapeutic targeting drug delivery system for prostate, ovarian, breast, and cervical cancers [abstract]. In: Proceedings of the Fifth AACR Conference on The Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2012 Oct 27-30; San Diego, CA. Philadelphia (PA): AACR; 2012. Abstract nr A37. Accepted to Cancer Epidemiology, Biomarkers & Prevention, February 2013

ABSTRACTS AND POSTER PRESENTATIONS (4 of 26 Selected)

• Saunders MR, Ma JY, Carreira V, Barlow V, Snook SS, Singer M, Otieno M, McDuffie Single cell analysis of translational regulators in acute pancreatitis. 40th Annual Meeting of the American College of Toxicology, Phoenix, AZ (Abstract and Poster), 2019.
• Saunders MR, Sadeho S, Carreira VS, Ma JY, Wang E, Barlow V, Glaab WE, Snook S, McDuffie In vivo to in vitro detection of miR216b-5p in models of acute pancreas toxicity. 39th Annual Meeting of the American College of Toxicology, West Palm Beach, Fl (Abstract and Poster), 2018.
• Saunders MR, Rabinowitz A, Ma JY, Carreira V, Vegas J, Varacallo L, Klass M, Barlow V, Snook S, McDuffie In vitro detection of acute pancreas toxicity in rats. 2018 La Jolla Science Day, Janssen Research & Development, San Diego, CA (Abstract and Poster).
• Rabinowitz A, Saunders MR, Kanerva J, Varacallo L, Carreira V, Rizzolio M, McDuffie Initial study of miRNAs as novel biomarkers for inducible pancreas acinar atrophy in Sprague Dawley Rats. SCCSOT Society of Toxicology Regional Meeting, San Diego, CA, 2017.
• Saunders MR, Ma JY, Zimmerman B, Chen Y, Vegas J, McDuffie Multiparametric validation of emerging translational pancreatic injury biomarkers. 37th Annual Meeting of the American College of Toxicology, Palm Springs, CA (Abstract and Poster), 2017; Janssen Scientist Mentoring and Diversity Program (SMDP) Scholar Poster Presentation to Janssen Research and Development Senior Leadership, Janssen Pharmaceutical Company of Johnson and Johnson, Spring House, PA. (Abstract and Poster) 2017.