The Latest In Cancer Research

After my postdoctoral fellowship at the Whitehead Institute/MIT, I went to Cold Spring Harbor Laboratory as a Senior Staff Investigate where we used yeast as a model organism to study novel mechanisms for regulation of cell cycle and cell growth. After 9 years, I moved to Wyeth Research in 1996 with a desire to translate science into treatment of human cancer. During this time, I led a group that developed Bosulif: an Abl/Src kinase inhibitor that is approved for relapsed and first line chronic myelogenous leukemia. Pfizer acquired Wyeth in 2009 and after serving as Vice President of Oncology Target Discovery within the Pfizer Oncology Research organization, I am currently Vice President of Oncology Scientific Strategy.

RESEARCH AREA

I manage coordination of Oncology Scientific Strategy and the project portfolio through collaboration with our three Chief Scientific Officers in the Oncology Research Division. We review external scientific innovation and business development partnering opportunities.

PUBLICATIONS

1. Epigenetic reprogramming by tumor-derived EZH2 gain-of-function mutations promotes aggressive 3D cell morphologies and enhances melanoma tumor growth.
   Oncotarget. 2015 6:2928-2938.
   Barsotti AM, Ryskin M, Zhong W, Zhang WG, Giannakou A, Loreth C, Diesl V, Follettie M, Golas J, Lee M, Nichols T, Fan C, Li G, Dann S, Fantin VR, Arndt K, Verhelle D, Rollins RA
   https://www.ncbi.nlm.nih.gov/pubmed/25671303
2. Molecular Pathways: Targeting the Cyclin D-CDK4/6 Axis for Cancer Treatment.
   Clinical Cancer Research. 2015 21(13): 1-6.
   VanArsdale T, Boshoff C, Arndt KT, Abraham RT
   https://www.ncbi.nlm.nih.gov/pubmed/25941111
3. Efficacy of SERD/SERM Hybrid-CDK4/6 inhibitor combinations in models of endocrine therapy resistant breast cancer.
   Clinical Cancer Research. 2015 21:5121-5130.
   Wardell SE, Ellis MJ, Alley HM, Eisele K, VanArsdale T, Dann SG, Arndt KT, Primeau T, Griffin E, Shao J, Crowder RJ, Lai JP, Norris JD, McDonnell DP, Li S.
   https://www.ncbi.nlm.nih.gov/pubmed/25991817

EDUCATION

Albright College, B.S. in Biochemistry, 1975
University of Pennsylvania, Ph.D. in Biochemistry, 1981
University of Pennsylvania, Postdoctoral Fellow, 1984
Whitehead Institute/MIT, Postdoctoral Fellow, 1988

AWARDS & HONORS

Sigma Xi Outstanding Ph.D. Dissertation Award, 1981
Wyeth Eagles Program (development program of top performers in R&D), 2002 – 2004
Winner: Pfizer Oncology B> "Colleague of the Year"; For discovery of BOSULIF for the treatment of CML, 2016

“It is a joy to work at Pfizer where every day you wake up and face the incredible challenges of learning many new things, the excitement of discovering new science, and the satisfaction of translating your efforts into therapies that extend the lives of cancer patients. There is no better job in the world.”

I joined Pfizer in 2017 and am a Senior Vice President in the Pfizer Early Oncology Research and Development Group. I focus on clinical development of early oncology assets. Prior to joining Pfizer, I was the Head of Early Development and Immunotherapy at Pharmacyclics (an Abbvie company). I was the clinical lead for the first Ibrutinib FDA approval in mantle cell lymphoma that was associated with a New England Journal of Medicine publication. I also led the Ibrutinib clinical team responsible for the first approved therapy in marginal zone lymphoma. As a faculty member of the Moffitt Cancer Center, I was the recipient of a Hollis Brownstein Research Grant and was recognized as a “Scientist to Watch” by the Leukemia Research Foundation. I also received multiple Clinical Scholars in Oncology Awards from the National Cancer Institute.

RESEARCH AREA(S)

My group (Early Oncology Development and Clinical Research-EODCR) is responsible for the early clinical development portfolio here at Pfizer. It consists of leaders from clinical development, clinical pharmacology, translational oncology, and other supportive areas. Our responsibility is to work closely with our discovery research and late development colleagues to transition our molecules from discovery to pivotal trial testing. In early development our responsibilities include performing first in human clinical trials with the goal of determining the safety profile and early efficacy signals of our novel molecules. Along with this, understanding the appropriate dose and schedule, indications to pursue, and combination partners to test are key deliverables from our group. In addition, a large focus on translational medicine is pursued in EODCR. Understanding pharmacokinetics, pharmacodynamics, resistance mechanisms, and subject selection strategies associated with our molecules is of paramount importance. The high functioning scientists and physicians as well as supporting staff that make up this group allow us to achieve these goals on a daily basis.

PUBLICATIONS

1. Targeting BTK with Ibrutinib in Relapsed/Refractory Marginal Zone Lymphoma A. Noy, S. de Vos, C. Thieblemont, P. Martin, C.R. Flowers, F. Morschhauser, G.P. Collins, S. Ma, M. Coleman, S. Peles, S. Smith, J.C. Barrientos, A. Smith, B. Munneke, I. Dimery, D.M. Beaupre, R. Chen, manuscript accepted in Blood, January 2017.
   https://www.ncbi.nlm.nih.gov/pubmed/28167659
2. The role of PIM1 in the ibrutinib-resistant ABC subtype of diffuse large B-cell lymphoma H.P. Kuo, S. A. Ezell, S. Hsieh, K.J. Schweighofer, L.W.K. Cheung, S.Wu, M. Apatira, M. Sirisawad, K. Eckert, Y. Liang, J. Hsu, C. Chen, D. Beaupre, and B. Y. Chang, manuscript accepted in American Journal of Cancer Research, October 2016.
   https://www.ncbi.nlm.nih.gov/pubmed/28428442
3. A first-in-human study of AMG 208, an oral MET inhibitor, in adult patients with advanced solid tumors D.S. Hong, P. Rosen, C. Lockhart, S. Fu, F. Janku, R. Kurzrock, R. Khan, B. Amore, I. Caudillo, H. Deng, Y.C. Hwang, R. Loberg, G. Ngarmchamnanrith, D.M. Beaupre, P. Lee, manuscript accepted in Oncotarget, June 2015.
   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4621921/
4. Long-term Follow-up of MCL Patients Treated with Single-agent Ibrutinib: Updated Safety and Efficacy Results M.L. Wang, K.A. Blum, P. Martin, A. Goy, R. Auer, B.S. Kahl, W. Jurczak, R.H. Advani, J.E. Romaguera, M. Williams, J.C. Barrientos, E. Chmielowska, J. Radford, S. Stilgenbauer, M. Dreyling, W.W. Jedrzejczak, P. Johnson, S.E. Spurgeon, L. Zhang, L. Baher, M. Cheng, D. Lee, D.M. Beaupre, S. Rule, manuscript accepted in Blood, April 2015.
   https://www.ncbi.nlm.nih.gov/pubmed/26059948
5. Targeting B Cell Receptor Signaling with Ibrutinib in Diffuse Large B Cell Lymphoma W.H. Wilson, R.M. Young, R. Schmitz, Y. Yang, S. Pittaluga, G. Wright, C.J. Lih, P. M. Williams, A. L. Shaffer, J. Gerecitano, S. De Vos, A. Goy, V. P. Kenkre, P. M. Barr, K. Blum, A. Shustov, R. Advani, N. H. Fowler, J. M. Vose, R. Elstrom, T. M. Habermann, J. C. Barrientos, J. McGreivy, B. Chang, F. Clow, D. Moussa, D. M. Beaupre, L. M. Staudt, manuscript accepted in Nature Medicine, April 2015.
   https://www.ncbi.nlm.nih.gov/pubmed/26193343

EDUCATION

University of Lowell, Biological Sciences, B.S., 1990
University of Lowell, Biological Sciences, M.S., 1990
University of Texas M.D., Anderson Cancer Center, Cancer Biology, Ph.D., 1997
University of Texas, Medicine, M.D., 1997

AWARDS & HONORS

Recipient of the Hollis Brownstein Research Grant
Recognized as a “Scientist to Watch” by the Leukemia Research Foundation
Received multiple Clinical Scholars in Oncology Awards from the National Cancer Institute

“I joined Pfizer due to the depth and promise of the Pfizer oncology early development portfolio. Pfizer is committed to leadership and excellence in the oncology space, which make innovative science and medicine a reality in our day to day activities.”

I joined the immuno-oncology efforts at Pfizer after 20 years in academia, initially as an Assistant Professor in the Division of Biological Science at the University of California, San Diego, and then at Sanford Burnham Prebys Medical Discovery Institute (SBP). At SBP, I was a Professor and Director of the Tumor Microenvironment and Cancer Immunology Program in the NCI-designated Cancer Center. Currently, I am the Chief Scientific Officer of the Cancer Immunology Discover (CID) Unit of Pfizer Oncology Research & Development, which is located in South San Francisco. Our driving interest is to understand how cells of the immune system are instructed or foiled in eradicating cancer cells within the tumor microenvironment. Understanding these cellular interactions at the molecular level holds the promise of developing novel immunotherapeutics that can confer durable anti-tumor responses.

RESEARCH AREA(S)

The Cancer Immunology Discovery (CID) team in South San Francisco is focused on the generation of large molecule immunotherapeutics that promote anti-tumor activity or counter immunosuppression in the tumor microenvironment. To achieve this goal, protein engineers, immunologists and cancer biologists at CID combine talents to advance projects from concept to clinical compounds. Protein engineering efforts are supported by a world class antibody generation program, and a commitment to effective biotherapeutic design that stresses both ingenuity and simplicity. Our immunologists and cancer biologists take a holistic approach to understanding the interplay of tumor, stromal and immune cells in the tumor microenvironment, striving to define the axes of intercellular communication that could be leveraged to generate novel therapeutics.

PUBLICATIONS

1. PDK1 regulates B cell differentiation and homeostasis. Proc. Nat. Acad. Sci. 2014 Jul 1;111(26):9573-8. doi: 10.1073/pnas.1314562111 Baracho, G.V., Zhu Z., Cato M.H., Jaren O.R., Hobeika E., Reth M., and Rickert, R.C.
   https://www.ncbi.nlm.nih.gov/pubmed/?term=24979759
2. Essential Role for Survivin in the Proliferative Expansion of Progenitor and Mature B Cells. J Immunol. 2016 Mar 1;196(5):2195-204. doi: 10.4049/jimmunol.1501690. Miletic A.V., Jellusova J., Cato M.H., Lee C.R., Baracho G.V., Conway E.M., and Rickert R.C.
   https://www.ncbi.nlm.nih.gov/pubmed/?term=26810226
3. Differing requirements for MALT1 function in peripheral B cell survival and differentiation. J Immunol. 2017 Feb 1;198(3):1066-1080. doi: 10.4049/jimmunol.1502518. Lee P., Zhu Z., Hachmann J., Nojima T., Kitamura D., Salvesen G.S., and Rickert R.C.
   https://www.ncbi.nlm.nih.gov/pubmed/?term=28031341
4. GSK3 is a metabolic checkpoint regulator in B cells. Nat Immunol. 2017 Mar;18(3):303-312. doi: 10.1038/ni.3664 Jellusova, J., Cato M.H., Apgar J.R., Ramezani-Rad P., Leung C., Chen C., Richardson A.D., Conner E.M., Benschop R.J., Woodgett J.R., and Rickert R.C.
   https://www.ncbi.nlm.nih.gov/pubmed/?term=28114292
5. Metabolic regulation of the humoral response. Immunity. 2017 May 16;46(5):743-755. doi: 10.1016/j.immuni.2017.04.009. Boothby M. and Rickert R.C.
   https://www.ncbi.nlm.nih.gov/pubmed/?term=28514675

EDUCATION

University of Wisconsin, Madison, Biological Sciences, B.S., 1986
University of North Carolina, Chapel Hill, Microbiology and Immunology, Ph.D., 1992
University of Cologne, Institute for Genetics, Postdoctoral Associate, 1997

AWARDS & HONORS

Fellowship recipient, Kölner Verein zur Förderung der Immunologie, 1995 – 1997
Fellowship recipient, Hellman Fellows Program for junior faculty, 2001 – 2002
Recipient, Concern Foundation Award, 2004 – 2006
American Cancer Society Research Scholar Award, 2004 – 2008
Outstanding alumnus, Department of Microbiology & Immunology, UNC-Chapel Hill, 2013

“The field of cancer immunology is in its infancy and yet we have already witnessed highly durable responses in some patients responding to check point inhibitors. While these treatments demonstrate the promise of immunotherapy, challenges remain to develop novel approaches that deliver effective, safe and durable treatments across tumor types. That’s the challenge we embrace every day and drives our discovery research.”

I am Vice President and Chief Scientific Officer of the Targeted Therapeutics Discovery Unit at the Oncology Research and Development, Pfizer. In this role, I lead the research group responsible for preclinical development of tumor-targeted therapeutics including antibody drug conjugate (ADCs), nanomedicines and bispecific T cell redirecting molecules. I joined Pfizer in 2009 as Associate Director, Oncology research Unit. Since 2009, in Pfizer, along with my colleagues, I built industry leading platforms and pipeline in targeted oncology arena and brought in several new technologies.

Prior to joining Pfizer, I led Pharmacology groups at Enzon Pharmaceuticals, NJ and Immunomedics Inc., NJ and developed several oncology-based drugs that are undergoing clinical evaluation. I have broad expertise in tumor-targeting strategies and biotherapeutics including immunotherapeutics, liposomal drug delivery system, nanoparticles, antisense oligonucleotide delivery and pegylation technologies. I am a well-recognized expert in the targeted therapeutics field and have given numerous lectures at national and international meetings.

I received my Bachelor's degree from the premier medical college of India, All India Institute of Medical Sciences. I was one of the two Indians selected to be awarded the prestigious British Chevening scholarship to pursue MS in Pharmacology from UK. I received my PhD in Pharmacology from University of Alberta on an AHFMR scholarship, in the lab of Theresa M Allen who pioneered the concept of Stealth liposomal technology that ultimately resulted in the development of Doxil®. My doctorate work focused on development of novel antibody-targeted liposomal drugs. I am an author of >50 scientific publications, book chapters and inventor/ co-inventor on >25 patents and have been a recipient of NIH SBIR grant. In 2017, I was recognized as one of the Healthcare Business Women Association Rising Star for Pfizer.

RESEARCH AREA(S)

I am the Chief Scientific Officer of the Targeted therapeutics Discovery group. The group is advancing the frontiers of cancer biology with a “toolbox” of differentiated technologies and targeted cancer therapies that selectively attack cancer cells while sparing normal healthy tissues. The group has deep expertise in the areas of various cancer-targeted modalities including nanomedicines, bioconjugates, antibody-drug conjugates (ADCs) and redirected T-cell bispecifics. Importantly, the group has contributed to the development of approved ADCs such as Mylotarg and Besponsa and advanced several other ADCs and redirected T-cell bispecifics in to early and late stage clinical development. The group has a deep biology focus on understanding innate immune sensing pathways and is combining the fields of immune-oncology and nanomedicine to develop novel platforms for delivering cancer immunotherapies.

PUBLICATIONS

1. Gemtuzumab Ozogamicin (GO) Inclusion to Induction Chemotherapy Eliminates Leukemic Initiating Cells and Significantly Improves Survival in Mouse Models of Acute Myeloid Leukemia. Neoplasia. 2018 Jan;20(1):1-11. Zhang CC, Yan Z, Pascual B, Jackson-Fisher A, Huang DS, Zong Q, Elliott M, Fan C, Huser N, Lee J, Sung M, Sapra P.
   https://www.ncbi.nlm.nih.gov/pubmed/29172076
2. Targeting the 5T4 oncofetal glycoprotein with an antibody drug conjugate (A1mcMMAF) improves survival in patient-derived xenograft models of acute lymphoblastic leukemia. Haematologica. 2017 Jun;102(6):1075-1084. McGinn OJ, Krishnan S, Bourquin JP, Sapra P, Dempsey C, Saha V, Stern PL.
   https://www.ncbi.nlm.nih.gov/pubmed/28341731
3. A PTK7-targeted antibody-drug conjugate reduces tumor-initiating cells and induces sustained tumor regressions. Science Translational Medicine- 2017 Jan 11;9(372). Damelin M, Bankovich A, Bernstein J, Lucas J, Chen L, Williams S, Park A, Aguilar J, Ernstoff E, Charati M, Dushin R, Aujay M, Lee C, Ramoth H, Milton M, Hampl J, Lazetic S, Pulito V, Rosfjord E, Sun Y, King L, Barletta F, Betts A, Guffroy M, Falahatpisheh H, O'Donnell CJ, Stull R, Pysz M, Escarpe P, Liu D, Foord O, Gerber HP, Sapra P, Dylla SJ.
   https://www.ncbi.nlm.nih.gov/pubmed/28077676
4. Enhanced Antitumor Activity of an Anti-5T4 Antibody-Drug Conjugate in Combination with PI3K/mTOR inhibitors or Taxanes. Clin Cancer Res. 2016 Jan 15;22(2):383-94. Shor B., Kahler J, Dougher M, Xu J, Mack M, Rosfjord E, Wang F, Melamud E, Sapra P.
   https://www.ncbi.nlm.nih.gov/pubmed/26319086
5. Damelin M, etal, , Sapra P, Gerber HP, Dylla SJ. Anti-EFNA4 Calicheamicin Conjugates Effectively Target Triple-Negative Breast and Ovarian Tumor-Initiating Cells to Result in Sustained Tumor Regressions. Clin Cancer Res. 2015 Sep 15;21(18):4165-73.
   https://www.ncbi.nlm.nih.gov/pubmed/26015513

EDUCATION

All India Institute of Medical Sciences (AIIMS) Delhi, India (Premier Medical Institute of India), B.Sc. Hons. Human Biology, 1998
University of Strathclyde, Glasgow, UK, M.Sc. Pharmacology, 1999
University of Alberta, Canada, Dept. of Pharmacology, Ph.D. Pharmacology, 2003

AWARDS & HONORS

Pfizer Individual performance awards, 2011 – 2016
Healthcare Business Women Association (HBA)
Rising Star for Pfizer, Featured on the cover page of the HBA Magazine “HBAdvantage”
Pfizer Pearl River Award, Pfizer 3R award
British Chevening Scholar awarded by the British Council and UK Foreign and Commonwealth Office
Alberta Heritage foundation for medical research award (AHFMR)

“At Pfizer we work collaboratively with a single mission of making difference in patients' lives. Drug discovery and development requires a solid teamwork effort. I am fortunate to be surrounded by extremely talented colleagues who have deep expertise and knowledge in various aspects of drug discovery and development and work collaboratively to bring medicines to our patients.”

I joined Pfizer in 2016 as CSO for Tumor Cell Biology, in the Oncology Research and Development Group. We are focused on the discovery and development of lead-in-class small molecule cancer therapies. Prior to Pfizer, I was Professor of Cell Biology; Associate Director of Basic Science for the Harold Simmons Comprehensive Cancer Center; and inaugural Director of the Cancer Intervention and Prevention Discovery program at UT Southwestern Medical Center.

The research in my academic group over the past 20 years has helped define the nature of oncogenic cell regulatory networks; decode the molecular architecture of mitogenic signaling pathways; enrich functional annotation of cancer genomes; and deliver genomics-guided cancer intervention target nominations. This work has been described in ~150 publications with over 12,000 citations and an H-index of 65. (http://www.ncbi.nlm.nih.gov)

RESEARCH AREA(S)

At Pfizer, our group pursues chemically addressable targets that intercept oncogenic signaling networks; modulate tumor/host interactions; and promote productive anti-tumor immune responses. We partner with colleagues in Medicinal Sciences, Drug Safety R&D, and Clinical Development to help deliver first-in-class small molecule drugs that benefit patient populations with unmet need.

PUBLICATIONS

1. Mode of Action and Pharmacogenomic Biomarkers for Exceptional Responders to Didemnin B.Nature Chemical Biology. 2015; 11(6):401-8.
   Potts MB, McMillan EA, Rosales TI, Kim HS, Ou YH, Toombs JE, Brekken RA, Minden MD, MacMillan JB, White MA.https://www.ncbi.nlm.nih.gov/pubmed/25867045
2. XPO1-Dependent Nuclear Export is a Druggable Vulnerability in KRAS-Mutant Lung Cancer.Nature. 2016; 538(7623):114-117.
   Kim J, McMillan E, Kim HS, Venkateswaran N, Makkar G, Rodriguez-Canales J, Villalobos P, Neggers JE, Mendiratta S, Wei S, Landesman Y, Senapedis W, Baloglu E, Chow CB, Frink RE, Gao B, Roth M, Minna JD, Daelemans D, Wistuba II, Posner BA, Scaglioni PP, White MA.
   https://www.ncbi.nlm.nih.gov/pubmed/27680702
3. Biomarker Accessible and Chemically Addressable Mechanistic Subtypes of BRAF Melanoma. Cancer Discovery. 2017; 7(8):832-851.
   Eskiocak B, McMillan EA, Mendiratta S, Kollipara RK, Zhang H, Humphries CG, Wang C, Garcia-Rodriguez J, Ding M, Zaman A, Rosales TI, Eskiocak U, Smith MP, Sudderth J, Komurov K, Deberardinis RJ, Wellbrock C, Davies MA, Wargo JA, Yu Y, De Brabander JK, Williams NS, Chin L, Rizos H, Long GV, Kittler R, White MA.
   https://www.ncbi.nlm.nih.gov/pubmed/28455392
4. Small-molecule TFEB pathway agonists that ameliorate metabolic syndrome in mice and extend C. elegans lifespan.
   Nature Communications. 2017; 8(1):2270.
   Wang C, Niederstrasser H, Douglas PM, Lin R, Jaramillo J, Li Y, Olswald NW, Zhou A, McMillan EA, Mendiratta S, Wang Z, Zhao T, Lin Z, Luo M, Huang G, Brekken RA, Posner BA, MacMillan JB, Gao J, White MA.
   https://www.ncbi.nlm.nih.gov/pubmed/29273768
5. Chemistry-First Approach for Nomination of Biomarker-Driven Intervention Opportunities in Lung Cancer.
   Cell. 2018. In Press.
   McMillan EA, Ryu M-J, Diep CH, Mendiratta S, Clemenceau JR, Vaden RM, Kim J-H, Motoyaji T, Covington KR, Peyton M, Huffman K, Wu X, Girard L, Sung Y, Chen P-H, Mallipedi PL, Lee JY, Hanson J, Yu Y, Park S, Sudderth J, DeSevo C, Muzny DM, Doddapaneni HV, Gazdar A, Gibbs RA, Hwang TH, Heymach JV, Wistuba I, Coombes KR, Williams NS, Wheeler DA, MacMillan JB, Deberardinis RJ, Roth MG, Posner BA, Minna JD, Kim HS, White MA.

EDUCATION

University of North Carolina, Chapel Hill, Biology, Ph.D., 1992
University of Iowa, Iowa City, Zoology, B.S., 1986

AWARDS & HONORS

Hortense and Morton Sanger Professorship in Oncology, 2009
Sherry Wigley Crow Cancer Research Endowed Chair in Honor of R Kirby, M.D., 2009 – 2016
Grant A. Dove Distinguished Chair for Research in Oncology, 2011 – 2016
NCI Outstanding Investigator Award, 2015

“Here at Pfizer, we participate in the ultimate transdisciplinary, multi-investigator, discovery and development campaign to deliver transformative therapies for patients that need them.”