(12a) Deconstructing the Tumor Microenvironment and Its Contribution to Metastasis

Despite aggressive surgical, radiological, and chemotherapeutic intervention, breast cancer recurrence remains a problem in up to 20% of patients. Most studies focus solely on tumors and tumor cells but often ignore the contribution of the normal tissues that surround and interact with tumor cells to disease progression. I am interested in combining my chemical and biomedical engineering expertise toward examining the mechanisms driving tumor recurrence and metastasis. I aim to study the relationship between tumor cells, normal tissues, and the immune system as a means of deconstructing the tumor microenvironment to understand how each component individually and as a whole contributes to metastasis and relapse after surgical and radiation treatment. The emphasis of my laboratory will be on developing bio-inspired in vitro models that recapitulate the tumor microenvironment by learning from in vivo mouse models. These studies will ultimately enable the design of optimized breast cancer therapeutics. I will build a program around analyzing the interplay between the physical, chemical, and biological cues that influence cancer metastasis and recurrence. Specifically, I will study (1) the collateral effect of radiation and surgery of normal tissues on tumor and immune cell migration patterns, (2) the molecular profiles of normal tissues wounded from therapy, and (3) the changes in the biomechanical properties of the tumor microenvironment and surrounding normal tissues following therapy. The idea that tissue response to therapeutic interventions may contribute to cancer recurrence is in its infancy. My research has the potential to challenge current paradigms about breast cancer treatment. My undergraduate and graduate studies provide me with the foundation to use biomimetic materials to study disease, and I will build on my strengths to design novel tumor microenvironment models in my independent research laboratory. My expertise has grown to encompass basic cancer biology, molecular imaging, biomechanical characterization of tissues, and in vivo experimental design through my postdoctoral work, which uniquely positions me to carry out research at the interface of engineering and medicine.

Successful Proposals:

K99/R00 Pathway to Independence Award, NIH/NCI; 2016-Present

Katherine McCormick Advanced Postdoctoral Fellowship; 2015-2016

T32 NIH NRSA Postdoctoral Fellowship in the Radiation Sciences; 2012-2013, 2015-2016

American Heart Association Founders Affiliate Predoctoral Fellowship; 2009-2011

Postdoctoral Project: â??The Role of the Immune System in Modulating Breast Tumor Cell Migration following Radiation-Induced Changes in the Tissue Microenvironmentâ?

Under the supervision of Edward Graves and Amato Giaccia, Department of Radiation Oncology, Stanford University 

Ph.D. Dissertation: â??Dual Antibody Functionalized Polyvinyl Alcohol and Alginate Hydrogels for Synergistic Endothelial Cell Adhesionâ?

Under the supervision of Debra Auguste, School of Engineering and Applied Sciences, Harvard University

Education:

Ph.D., Harvard University, Engineering Sciences, 2012

S.M., Harvard University, Engineering Sciences, 2007

S.B., Massachusetts Institute of Technology, Chemical Engineering, 2006

Selected Peer-Reviewed Publications:

1. Rafat M, Ali R, Graves EE. Imaging Radiation Response in Tumor and Normal Tissue. American Journal of Nuclear Medicine and Molecular Imaging. 2015; 5(4): 317-332 (Review).
2. You JO*, Rafat M*, Almeda D, Maldonado N, Guo P, Nabzdyk CS, Chun M, LoGerfo FW, Hutchinson JW, Pradhan-Nabzdyk LK, Auguste DT. pH-Responsive Scaffolds Generate a Pro-Healing Response. Biomaterials. 2015; 57: 22-32. *Equal contribution. Highlighted in Materials Today. May 21, 2015.
3. Vilalta M, Rafat M, Giaccia AJ, Graves EE. Recruitment of Circulating Breast Cancer Cells Is Stimulated by Radiotherapy. Cell Reports. 2014; 8(2): 402-409.
4. Rafat M, Rotenstein L, Hu J, Auguste DT. Engineered Endothelial Cell Adhesion via VCAM1 and E-selectin Antibody-Presenting Alginate Hydrogels. Acta Biomaterialia. 2012; 8(7): 2697-2703.
5. Rafat M, Rotenstein L, You JO, Auguste DT. Dual Functionalized PVA Hydrogels that Adhere Endothelial Cells Synergistically. Biomaterials. 2012; 33(15): 3880-3886.

Teaching Interests:

Teaching Experience

I held two teaching fellow positions during graduate school, where I earned Certificates of Distinction in Teaching. I was a Teaching Fellow in 2007 for a graduate-level course in drug delivery that focused on engineering solutions for delivering drugs to specific sites in the body. In 2009, I served as the Head Teaching Fellow for an undergraduate-level introductory course in fluid mechanics and transport processes. During my postdoctoral fellowship in 2014, I participated in the Stanford Pre-Collegiate Studies Program, where I lectured students in the Cancer Biology section of the Topics in Biosciences and Biotechnology module.

Mentoring Experience

I have extensive experience teaching and mentoring students in a research capacity. Through the National Science Foundation Research Experiences for Undergraduates (REU) program, I have mentored three students since 2007. I also advised three undergraduate students on their theses while at Harvard. My mentees contributed to co-authored publications and multiple conference presentations. At Stanford, I have supervised a summer veterinary student and a clinical research assistant who was interested in receiving wet lab training before attending medical school. I am currently supervising an undergraduate student on her own project. I emphasize critical thinking and challenge students to be active in the design, implementation, and analysis of their research. Mentoring students has been incredibly rewarding; I am eager to continue advising and instructing students as a junior faculty member.

Teaching Philosophy

My previous teaching experiences have given me a realistic sense of how to teach classes and mentor students in the future. As a professor, I will give students the necessary tools for developing analytical thinking skills and to solve problems beyond cookie-cutter solutions. I will structure classes using a combination of hands-on learning through laboratory projects as well as reading the current literature for students to gain an understanding of cutting-edge research. I will also expose students to problems with unknown solutions to challenge them to think critically and devise solutions creatively.