Department of Developmental & Molecular Biology

Jeffrey Pollard's Laboratory

Dr. Jeffrey W. Pollard

Director, Center for the Study of Reproductive Biology and Women's Health
Deputy Director, Albert Einstein Cancer Center
Professor, Departments of Developmental and Molecular Biology
Professor, Departments of Obstetrics & Gynecology and Women's Health
Louis Goldstein Swan Chair in Women's Cancer Research
Faculty Supervisor, Transgenic Mouse Facility
 

Room 607 Chanin
Tel: 718.430.2090
Fax: 718.430.8567
pollard@einstein.yu.edu  

Jeffrey W. Pollard's Laboratory personnel 

 

  

 

"Dr. Pollard giving opening keynote address at the International Tumor Microenvironment meeting in Versailles"

 

Bio:

Dr. Jeffrey W. Pollard is the Director of the Specialized Center in Reproduction and Infertility Research. He is The Louis Goldstein Swan Chair in Women's Cancer Research, Director of the Center for the Study of Reproductive Biology and Women's Health and Deputy Director of the Cancer Center at Einstein, Professor of Developmental and Molecular Biology and of Obstetrics & Gynecology and Women’s Health.

He has been Chair in the “Reproductive Tract” and “Mammary Gland” Gordon Conferences as well as being Chair of the Publication Committee of the Society for the Study of Reproductive Biology. He is and has been on the editorial board of many journals including “Biology of Reproduction” “Molecular Oncology” and “The Journal of Mammary Gland Biology and Neoplasia”. He also serves on many Scientific Advisory Boards including the Campbell Center in Toronto and The Program in Tumor Microenvironment at MIT. He has been awarded the Darwin Lectureship of the British Association of the Advancement of Science, received a Monique Weill-Caulieraward, he was the Betty and Sheldon E Feinberg Scholar in Cancer Research and is a member of the Faculty of 1000 in the Reproductive Immunology section. He is a speaker at a wide range of national and international conferences often in a Keynote role. Recently he was an invited speaker for the opening of the new Rosalyn Institute in Edinburgh and at the 100th anniversary of Metchnikoff’s Nobel Prize and 120th of the Pasteur Institute.

He has had a long history in the study of Reproductive Biology that has included studies on neuroendocrine regulation of puberty andestrus cycling, ovarian function, particularly germ cell development andmeiosis, reproductive immunity and the mechanism of action of female sexsteroid hormones. He also has a particular interest in the roles of macrophagein reproduction, development and disease. He runs an extremely active lab thathas been continuously funded for over 30 years and is in the top 1% cited in Biomedicine. It has strong translational components and along with post-doctoral fellows and graduate students always hosts clinical fellows andfaculty. In the last year five students have graduated from his laboratory with Ph.D. degrees.
 

My laboratory has two overlapping but distinct areas of research: 

1.  The Tumor Microenvironment  

2. Mechanisms of action of estrogen and progesterone in controlling cell division in vivo. 

We take a broad approached to studying these problems but with a central focus on using mouse genetics to dissect the molecular mechanisms in vivo.  We also use high throughput methods such as DNA microarray based approaches and novel in vivo imaging methods to define cellular interactions and the novel signaling pathways involved in these interactions. Furthermore, we concentrate on translating our fundamental observations to clinical practice. To cover these areas we have a well funded laboratory staffed by senior fellows, post-doctoral fellows, graduate students, clinical fellows and technicians that allows us to cover many different areas of expertise. In the last year and a half five students graduated from the laboratory including two MD/PhD students.  We are also well represented both by publications with over a dozen front covers of journals representing our research as well as coverage in major text books of cell biology and cancer. Furthermore in the last year Dr. Pollard gave invited talks at fifteen different conferences ranging in topics from cancer to implantation. 

A brief synopsis of the Pollard’s labs research interests is given below:  

(1) Tumor Associated Macrophages Promote Tumor Progression and Metastasis  

Many hematopoietic cells, particularly those of the innate immune system, populate the tumor microenvironment. Of these both clinical observations and our genetic experiments in mouse models of beast cancer have indicated that macrophages play a pivotal role in enhancing tumor progression and metastatic potential (Joyce and Pollard, 2009). Our mechanistic studies indicate that these tumor-associated macrophages regulate the angiogenic switch required for the malignant transition and also promote tumor cell invasion, migration and intravasation through reciprocal EGF and CSF-1 signaling (Condeelis and Pollard, 2006; Lin and Pollard, 2007; Pollard, 2004, 2008, 2009). Furthermore, we have recently identified a sub-population on macrophages that are required for metastatic seeding and persistent growth at distant sites (Qian et al., 2009). 

The lab is focused upon defining unique sub-sets of macrophages that promote different aspects of tumor progression and metastasis and in elucidating the fundamental mechanisms behind these actions. We are using novel mouse genetic and virus based tools developed in our lab to interfere with signaling pathways in vivo to define the function of these pathways in the metastatic progression of tumors. Further we are studying the evolution of the immune system during tumor development to determine how the tumors escape from being rejected and focus on the role of macrophages in these processes. The identification of these mechanisms of tumor promotion by macrophages will allow us to novel therapeutic approaches to inhibit tumor progression and malignancy. 

(2) Regulation of cell proliferation by female sex steroid hormones.  

Exposure to estrogen is the major risk factor for endometrial and breast cancer.  This carcinogenic effect is thought to be due to the induction by this hormone of continuous cycles of epithelial cell proliferation that allows the fixation of spontaneously occurring oncogenic mutations.  In contrast progesterone exposure reduces the risk of these cancers.  In the uterus of mice and humans estrogen stimulates epithelial cell proliferation while progesterone completely blocks this estrogen-induced proliferation.  We have used biochemical and genetic approaches in mice to identify the mechanisms of action of these sex steroid hormones.  We have identified two pathways stimulated by estrogen and inhibited by progesterone that are required for the estrogen-induced mitogenic effect.  The first of these is through IGF-1 signaling activating cyclin D1 mobilization into the nucleus while the second involves licensing of DNA replication through the regulation of the function of Minichromosome Maintenance proteins (MCMs) (Pan et al., 2006; Zhu and Pollard, 2007).  To extend these studies to humans we have developed a program to obtain endometrial biopsies and have used laser capture microdissection of epithelial tissue to confirm similarities in hormone control of gene transcription between the two species.  Further we have been able to xenograft human endometrial tissue into mice where it forms functional endometrial structures that responds to humans and which allows for biochemical analysis (Polotsky et al., 2009).  Using all these techniques, we have identified novel hormone regulated signaling pathways that are deregulated in human endometrial proliferative diseases such as endometriosis and cancer and that may therefore act as therapeutic targets. 

Current studies are to further elucidate the downstream cascade of transcriptional regulatory proteins that are induced by estrogen and progesterone that are involved in the regulation of cell proliferation.  We also have a significant set of studies in understanding the roles of Micro RNAs in the regulation of hormone action.  These are pursued at the biochemical and genetic levels and we are currently developing novel genetic tools in which to study sex steroid hormone action.

 

Selected References: PubMedLink

Joyce, J.A., and Pollard, J.W. (2009). Microenvironmental regulation of metastasis. Nat Rev Cancer 9, 239-252.

Pollard, J.W. (2009). Trophic macrophages in development and disease. Nature reviews Immunology 9, 259-270.

Polotsky, A.J., Zhu, L., Santoro, N., and Pollard, J.W. (2009). Lithium chloride treatment induces epithelial cell proliferation in xenografted human endometrium. Human Reproduction  24, 1960-1967.

Qian, B., Deng, Y., Im, J.H., Muschel, R.J., Zou, Y., Li, J., Lang, R.A., and Pollard, J.W. (2009). A distinct macrophage population mediates metastatic breast cancer cell extravasation, establishment and growth. PLoS ONE 4, e6562.

Pollard, J.W. (2008). Macrophages define the invasive microenvironment in breast cancer. Journal of Leukocyte Biology 84, 623-630.

Zhu, L., and Pollard, J.W. (2007). Estradiol-17beta regulates mouse uterine epithelial cell proliferation through insulin-like growth factor 1 signaling. Proceedings of the National Academy of Sciences of the United States of America 104, 15847-15851.

Lin, E.Y., and Pollard, J.W. (2007). Tumor-associated macrophages press the angiogenic switch in breast cancer. Cancer Research 67, 5064-5066.

Condeelis, J., and Pollard, J.W. (2006). Macrophages: obligate partners for tumor cell migration, invasion, and metastasis. Cell 124, 263-266.

Pan, H., Deng, Y., and Pollard, J.W. (2006). Progesterone blocks Estrogen-induced DNA synthesis through inhibition of Replication Licensing. Proceedings of the National Academy of Sciences of the United States of America 103, 14021-14026.

Pollard, J.W. (2004). Tumor educated macrophages promote tumor progression and metastasis. Nature Reviews Cancer 4, 71 - 78.

 

 

Personnel

Jeffrey Pollard's Laboratory

 
Position  Name 
Ext. 
Email 
Lab 
Associate (DMB) & Asst Prof (Ob/Gyn) Liyin Zhu
3138
lzhu@einstein.yu.edu 
C 636
Asst Prof (Ob/Gyn) Alex Polotsky
3138
apolotsk@einstein.yu.edu 
C 607
Postdoc Evelyn Aranda
3138
earanda@einstein.yu.edu 
C 607
Postdoc Sanhita Ray
3138
sray@einstein.yu.edu 
C 607
Postdoc Binzhi Qian
3138
bqian@einstein.yu.edu 
C 607
Postdoc Roy Noy
3138

rnoy@einstein.yu.edu 

C 607
Student Yuxiang Wang
3138
yuxwang@einstein.yu.edu 
C 607
REI Fellow Marie Menke 
3138
mnmenke@gmail.com 
C 607
Fellow Satu Kuokkanen 
3138
skuokkanen@verizon.net 
C 607
Administrator Yolanda Cassidy
2819
cassidy@einstein.yu.edu 
C 601

Transgenic Mouse Facility

 
Position  Name 
Ext. 
Email 
Lab 
Prin. Associate Ken Chen
1106
kchen@einstein.yu.edu 
Price center B110
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