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MICROENVIRONMENT EVOLUTION AND THERAPEUTIC CONSEQUENCES IN METASTATIC PROGRESSION

Summer 2022


Project Background

Metastases are responsible for a majority of cancer-related deaths. Inter-tumoral heterogeneity; the fact that every tumor has distinct genetic, epigenetic, and biophysical features, poses a challenge for effective cancer therapy. While genetic and epigenetic variants that influence a tumor’s response to targeted therapy have received great attention, comparatively less is known about the physiological heterogeneities in the metastatic TME. Aberrant blood vessels, hypoxia and dysregulated matrix, influence the delivery and hence, efficacy of administered chemo-, and immuno-therapies. Surprisingly, despite their critical roles in cancer progression, treatment response and resistance, our understanding of the vascular and stromal heterogeneities of metastatic TME remains limited.

The overarching goals of this project are to: (1) systematically catalogue the dynamic changes that occur in the vascular and stromal microenvironment of the metastatic tumors as they grow from single cell to micro- and macro-metastases, and (2) to evaluate how these changes correlate with and impact the delivery and therapeutic efficacy of clinical anti-cancer therapies.

We will evaluate these dynamic evolution of metastatic vascular and stromal niche in the context of experimental models of pulmonary metastases of triple negative breast cancer, with the expectation that findings from these studies will lead to multi-organ, multi-tumor investigations in advanced models of metastatic cancers.

Student Role

Student role and responsibilities include:

  1. Image processing, analysis and quantification of multiplexed immunofluorescence data from high resolution confocal tissue microscopy, using advanced image analysis software.
  2. Organizing and presenting their results through oral and written presentations during lab meetings. Students will assist in literature search, writing manuscripts and preparing presentations. Contributions will be recognized through co-authorships, as applicable.
  3. Establishing and maintaining cultures for various mammalian cell lines. The student will learn and use techniques like cell culture, microscopy, flow cytometry etc.
  4. Assisting the PI and other lab members in in vitro and in vivo experiments after proper training.
  5. Being proactive, curious, driven, and respectful in the lab.

Student Learning Outcomes and Benefits

The student will have the benefit to work and learn in a highly multidisciplinary research environment to gain experience in basic and translational biomedical cancer research. The student will get direct hands-on experience with cell culture and related in vitro experimental procedures. There are opportunities to learn cutting-edge imaging methods and software. The student will present progress report in weekly lab meetings; thus, they will have exceptional training in critical evaluation of the data, communication skills, and problem solving. These skills are essential in career development and advancement. Through these meetings and feedback, the student will also find support to prepare and practice for their final presentation for the Undergraduate Research Symposium. The students will be encouraged to engage in other projects and collaborate with other members to expose them to a broad range of biomedical research and diversify their scientific experiences.

 

Shreya Goel

Assistant Professor
Pharmacy
Pharmaceutics & Pharmaceutical Chemistry

We develop and implement advanced multimodal molecular imaging and nanobioengineering tools to refine the way we visualize, treat and manage cancer and other diseases. We apply multiscale imaging technologies to 1) quantitatively visualize the pharmacokinetics and biodistribution of nano- and macromolecular therapies to better understand their in vivo interactions, and, 2) develop predictive and pharmacodynamic cues to improve treatment outcomes through a personalized diagnostic approach.

Mentoring Philosophy

My mentoring philosophy is based on effective communication, scientific excellence and integrity, and creating an inclusive and diverse environment to foster a collegial and collaborative space for all lab members. I believe that an effective mentor provides resources and background to the students to pursue and conduct their research. But more importantly, they provide the students the freedom to ask questions, and the tools and guidance to seek answers to those questions. My responsibility is to provide my mentees as many opportunities as possible, for them to pursue and excel in their scientific and professional goals. I provide one-on-one mentoring to my students that is tailored to their individual personalities, preferences, intellectual and professional goals. I meet with the students once weekly on an individual basis. We have biweekly lab meetings where everyone is encouraged to present their progress in a friendly setting. This not only provides the students with universal professional skills like critical thinking, oral and written presentation and public speaking, but also encourages them to think beyond their individual projects through exposure to diverse research areas. I maintain long-lasting professional relationships with my mentees and continue to support and advocate for them as they navigate their careers, even after transition to different institutions, industries, or even countries.