Shannon T. Bailey, Ph.D.
Dana-Farber Cancer Institute

As a college student at the Pennsylvania State University, my scientific curiosity led me to join Dr. Mark Guiltinan's lab studying a transcription factor in maize. This experience allowed me to become skilled at various lab techniques as well as learn how to formulate and explore scientific questions. Though I explored the idea of practicing medicine, it was here that I found my calling as a scientist.

Prior to matriculation in graduate school, I worked in the laboratory of Dr. Mitchell A. Lazar at the University of Pennsylvania as a research specialist for two and a half years. In the Lazar lab, my research mainly focused on the study of the activation of the nuclear hormone receptor PPAR by a class of anti-diabetic compounds known as thiazolidinediones (TZDs). In addition to the activation of PPAR my research also involved the exploration of transcriptional targets suppressed by PPAR in response to TZDs in fat tissue. It was in these studies that I cloned and initially characterized the novel fat cell secreted hormone, resistin. Though much research still remains to establish the exact physiological function of resistin, this hormone has been shown to play a role in obesity-related diabetes.

After such a rewarding experience at Penn, I decided to further my pursuits by attending graduate school at Yale University in the Department of Cellular and Molecular Physiology where I worked in the laboratory of Dr. Sankar Ghosh, a pioneer in the NF- B field. NF- B is a transcription factor that is important in many different biological contexts, including breast cancer. My dissertation focused on the nature of the constitutive NF- B activity found in estrogen receptor negative breast cancer cells. We examined human mammary epithelial tumor cell lines to characterize their NF- B activity using a number of different approaches. We observed that NF- B is highly active in estrogen receptor negative mammary epithelial cell lines and found that the primary signal that initiates this activation cascade may be DNA damage.

Using all these experiences as a backdrop, I decided to come to the renowned Dana-Farber Cancer Institute to continue to study breast cancer in the laboratory of Dr. Myles Brown. The Brown lab has made many contributions to the understanding of estrogen receptor biology as well as other nuclear hormone receptors. More recently, the lab has employed the use of the human genome to gain even more insight into how the estrogen receptor is regulated, potentially leading to new and better ways of treating breast cancer.

My research in the Brown lab focuses on how the estrogen receptor influences the cell death process. In order for any cancer cell to grow, it must be able to circumvent physiological mechanisms that prevent abnormal growth. My research aims to identify the mechanism by which this occurs in ER positive breast cancer cells. Identifying how estrogen affects gene regulation in a breast cell is essential to providing better treatment of breast cancer. Combining the studies of both the estrogen receptor and its regulation of cell death pathways promises to lead to an even greater understanding of not only estrogen receptor positive cancers but may also provide insight into other malignancies as well.

My future aspirations include establishing a career as an independent academic breast cancer researcher. As an African-American, I always wanted to pursue research that was not only beneficial to the greater good but could also have a significant impact on my community. The incidence of triple-negative breast cancer in African-American women is significantly high and my future plans include trying to make strides in treatment of this deadly form of breast cancer.

I am originally from Wiesbaden, Germany, but moved to the UK in 1999 to study Molecular Genetics at the University of Sussex. After completing my Bachelor of Science with First Class Honours, I joined the cell biology graduate program at the Medical Research Council's Laboratory of Molecular Cell Biology at University College London. Under the mentorship of Dr. Yasuyuki Fujita, my research focused on expanding our knowledge of the molecular machinery that controls cell polarity, a fundamental cellular process that is commonly perturbed in cancer cells.

We identified and characterized a novel biochemical regulatory mechanism that controls the activity of a key cell polarity protein, which also functions to suppress tumor growth. My graduate research allowed me to gain a thorough experience in biochemical and cell biological techniques and it gave me the opportunity to design experiments aimed at unraveling the complexities of the molecular processes that govern cellular behavior. However, towards the end of my PhD it became clear to me that to achieve my long-term goal of conducting research that will translate into better treatment options for cancer patients, I would have to gain experience in advanced animal models of cancer and investigate how aberrations in the molecular machinery eventually lead to the critical endpoint - tumorigenesis.

This desire to work in a lab at the forefront of cancer genetics and animal models of cancer led me to a postdoctoral position within Dr. Scott Lowe's group at Cold Spring Harbor Laboratory. My project centers on discovering and validating novel breast cancer genes that we believe will point towards novel therapeutic targets or serve as prognostic indicators in the clinic. To achieve this aim, we are combining a comprehensive data set of mutations that occur in human breast cancer samples, with an animal model of the disease that allows us to shut off each of these genes in breast cells, thereby modeling the effect of a mutation. The idea is to find all the mutated genes that directly contribute to breast cancer formation amongst the vast number of genetic alterations found in cancer. In essence, we are using our advanced mouse model of breast cancer as a filter to sift out the disease relevant genes whole loss of function contributes to breast cancer development and in turn may point towards molecules that can be targeted therapeutically or predict disease outcome.

Extending from Dr. Lowe's laboratory, Cold Spring Harbor Laboratory provides me with an optimal combination of resources, collaboration and teaching that makes it the ideal environment for my scientific training as a breast cancer researcher. I am grateful for the support of the Terri Brodeur Breast Cancer Foundation and believe it will be a vital facilitator towards achieving my ultimate career objective: To lead an independent laboratory at the forefront of breast cancer research, a lab that is actively involved in the pursuit of knowledge that translates into improved treatment options for patients.

I was born in Kozan, a typical eastern Mediterranean city of Turkey near Adana. I received my M.D. degree from Marmara University School of Medicine, Istanbul in 2000 and my Ph.D. degree from Sabanci University Biological Sciences and Bioengineering Program, Istanbul in 2006. During my Ph.D. studies, I tried to identify cell death pathways activated by lipid peroxidation end products. Following my visit to Cancer Center Karolinska with a support from EACR (European Association for Cancer Research) in 2005, I decided to pursue a career in cancer biology, mainly focused on breast cancer because of the lack of extensive research specifically concentrated on apoptotic defects and breast cancer therapy. In the last year of my Ph.D. education, I was granted a research fellowship from Terry Fox Cancer Research Fund for a project on Bcl-2 family proteins and breast cancer.

After finishing my Ph.D., I joined as a research fellow in the laboratory of Dr. Anthony Letai at Dana-Farber Cancer Institute. Dr. Letai is recognized as an innovative leader at the intersection of apoptosis and cancer, particularly in the research of Bcl-2 proteins. In his laboratory, a considerable amount of effort has been devoted to understanding basic mechanisms of cancer cell death. Additionally, the excellent training environment of Letai lab and Dana-Farber Cancer Institute with its Breast Program at Dana-Farber/Harvard Cancer Center, full array of molecular and cellular biology research laboratories and equipment provides a dedicated and collaborative environment for self-development and innovative breast cancer research.

Chemotherapy plays a critical role in the management of both limited and advanced breast cancer. All too often, however, the tumor responds poorly to chemotherapy, or an initial response is followed by ultimate relapse and resistance. Thereby, resistance to chemotherapy is a major problem in the fight against breast cancer. My current research at Letai lab involves exploring the pathways of cell death activated by chemotherapeutics in breast cancer cells and the regulation of these pathways by Bcl-2 proteins. By obtaining a more detailed understanding of the basic molecular mechanisms involved, we hope to be able to design new treatment plans to improve response and overcome resistance to therapy in breast cancer patients.

As an early career scientist, my future career aim is to establish my own research laboratory, with a capacity for innovation and ideas without borders to develop novel therapeutics targeted against breast cancer. The funding from the Terri Brodeur Breast Cancer Foundation gives me the opportunity to continue my work towards understanding how chemotherapy kills breast cancer cells and to participate in the "walk against breast cancer".

I was born in a rural countryside in Hubei province, located in the central part of China. In our village, none of us received education beyond high school, including my parents. My mom never went to any school. Despite all kinds of difficulties, I was recruited by the prestigious Wuhan University to pursue my bachelor's degree in Biochemistry with the freshman's scholarship. After graduation from college with distinction in 2001, I was offered a fellowship from the graduate program in University of Pittsburgh School of Medicine. My Ph.D research was conducted in the well-known surgeon scientist Dr. Jennifer Rubin Grandis' lab. My thesis research focused on investigating the molecular mechanism of epidermal growth factor receptor (EGFR) activation by gastrin releasing peptide (GRP)/gastrin releasing peptide receptor (GRPR) in head and neck cancer. More importantly, these studies provide some combination targeting strategies that can potentially enhance the anti-tumor efficacy of EGFR monotherapy in cancer.

After getting my Ph.D from pharmacology program in 2005, I clearly realized that I want to devote my career to cancer research. The very obvious reason for me is that several relatives and friends from where I grew up in the rural countryside died of cancer. The sad part is that the diagnosis of cancer was too late and most of them even did not realize they had cancer before they passed away. For me, first of all, I want to make myself useful by promoting the awareness of cancer to people, especially to those underprivileged people. Second, I want to contribute as much as I can to better understanding of cancer progression and effective cancer therapy. For these reasons, I joined the laboratory of Dr. William Kaelin at Dana-Farber Cancer Institute/Howard Hughes Medical Institute. Dr. Kaelin is a prestigious cancer researcher in the field of tumor suppressors, such as von Hippel Lindau (VHL), Rb, and p53. Specifically, he is interested in understanding how mutation of tumor suppressors causes cancer. My research focuses on EglN2, one important player of VHL tumor suppressor pathway. Inactivating EglN2 does not affect normal cells but significantly diminishes the proliferation of human breast cancer cells. This work should motivate the development of drugs that inhibit EglN2, especially in estrogen receptor (ER) positive breast caner therapy.

With the generous funding from the Terri Brodeur Breast Cancer Foundation, I hope that my research can shed light on the molecular mechanism by which EglN2 contributes to breast cancer progression. My long term goal to validate the therapeutic potential of EglN2 for breast cancer treatment, which will provide a new avenue for breast cancer treatment.