Author: Sanidhya Tripathi Major: Biomedical Engineering
Sanidhya Tripathi with the state-of-the-art Raman spectroscopy system in the Rajaram Lab
My name is Sani Tripathi and I am currently a rising senior majoring in Biomedical Engineering (College of Engineering) with a minor in Medical Humanities at the University of Arkansas. I received an Honors College Research Grant for the 2021 school year (Spring and Fall). The mentor for my project which is entitled “Determining the sensitivity of Raman spectroscopy to differences in tumor bioenergetics in vivo in Triple-Negative Breast Cancer” is Dr. Narasimhan Rajaram who is an Associate Professor in the Department of Biomedical Engineering.
Dr. Rajaram’s lab, the Laboratory for Functional Optical Imaging and Spectroscopy at the University of Arkansas, is interested in using various optical imaging techniques to investigate changes in the tumor microenvironment in response to treatment. The lab has conducted numerous studies to identify hallmarks of cancer treatment resistance, recurrence, and metastasis. By using these clinically compatible optical technologies which are noninvasive, personalized treatment plans can be delivered to patients by their physicians. My funded project deals with using Raman spectroscopy (RS), a technique capable of probing biomolecular changes of cells and tissues, to find differences in Triple-Negative Breast Cancer (TNBC) tumors that undergo different metabolic pathways (glycolysis or oxidative phosphorylation). This work can prove to be a pivotal step in establishing RS as a tool to evaluate response to therapeutics that target cell metabolism.
Before I arrived at the University of Arkansas, I was heavily involved in research as a high school student receiving success at both national and international competitions. Having conducted work at the both University of Arkansas – Little Rock (UA-Little Rock) and the University of Arkansas for Medical Sciences (UAMS), I was fortunate to have mentors that gave me a chance at a young age to explore different areas of science. Once I started my freshman year here in Fayetteville, I wanted to continue to work in a lab due to my positive experience at my other stops. Within the first month of my time on campus, I was able to join Dr. Rajaram’s lab to conduct a project which I used to present at the 11th Annual Honors Engineering Symposium on campus. This research was conducted alongside another Biomedical Engineering undergraduate student who was also in the same class as me (Honors Research Experience). Through this class, I was able to get plugged into undergraduate research at an early point in my time in college. The first project I did in the Rajaram Lab focused on using RS which is where I grew to love the technique and its application in cancer research.
After my first project in the lab as well as helping other graduate students with their work, in my junior year it had come time to develop an individual project which I could apply for funding for as well as use to complete my honors thesis. For this, I spoke with Dr. Rajaram several times during our individual meetings to brainstorm ideas. We ultimately decided on investigating in the metabolism space given the fact that not much work had been done by previous researchers as observed in the literature. In addition, the Rajaram Lab at the time had just published a paper in collaboration with researchers from Johns Hopkins University where they used RS to reveal key biomolecular changes in radiation resistance and sensitive tumors that were treated with radiation therapy. To build off this work, metabolism was also an area of interest so we decided that my project could study using RS for that.
My project deals with a phenomenon known as metabolic reprogramming. Metabolic reprogramming is a prominent hallmark of changes in the tumor microenvironment in which tumors exhibit different metabolic phenotypes in order to fuel their proliferation/progression in the body. Aerobic glycolysis (metabolism of glucose to lactate) has been shown to provide an early proliferative advantage; however, studies in TNBC have shown that breast cancer cells can favor mitochondrial oxidative phosphorylation (OXPHOS) to efficiently generate ATP and result in a migratory phenotype. This phenomenon is directly linked to a condition such as TNBC. TNBC is an aggressive subtype of breast cancer that is characterized by a lack of progesterone receptor (PR), estrogen receptor (ER), and human epidermal growth factor (HER2) expression. Accounting for approximately 15% of breast cancer cases, TNBC is associated with an aggressive phenotype and poor prognosis. Even though patients have been shown to benefit from neoadjuvant chemotherapy, they still face high recurrence and death rates compared to non-TNBC cancers especially within the first 2 years of diagnosis. Furthermore, TNBC tumors often develop resistance to chemotherapeutic drugs. This situation persists due to the limited understanding of the metastatic progression of breast cancer. Factors such as the inability to predict which tumors are prone to metastatic progression and incomplete knowledge of metabolic/molecular/physiological adaptations for cancer cells to survive have caused limited advancement in the field. Therefore, there remains an urgent need to develop novel strategies to improve the abysmal treatment rates in the clinic. The goal of my project is to utilize RS to examine tumor bioenergetics in vivo in TNBC. By doing this, RS can be directly translated to the clinic to not only identify viable candidates for therapy but also evaluate response during therapy. This large-scale impact is what excites me most about the project and am motivated to continue in this line of work after I graduate.
During the course of my proposal for the Honors College Research Grant as well as my initial experiments in the lab this past semester, Dr. Rajaram played an instrumental role in giving me suggestions and advice on how I could approach certain things. Having an extensive amount of experience, Dr. Rajaram has been in the biomedical optics space for a long time so all of his tips to be were valuable at all times. It allowed me to grow my skills both in the lab as well as outside the lab in terms of how to think about scientific problems and ask meaningful questions. In addition to Dr. Rajaram’s help, I received help from the other graduate students in the lab including Sina Dadgar (Graduated December 2020), April Jules, and Joel Rodriguez Troncoso and I can not thank them enough for their support throughout this semester.
As I use the Fall 2021 semester to continue to work on my project, I have been thinking for some time about what my future plans are. Having been involved in research labs since 2016, I have had the opportunity to conduct research (basic science, translational, and clinical) at various places including Yale, UC San Diego, NIH, and more. These experiences have all expanded my laboratory skillset and motivated me to pursue a Ph.D. in Biomedical Engineering. In addition, I will be headed to Vanderbilt University to conduct biophotonics research which I will believe will solidify the kind of research I want to pursue in graduate school. I would like to thank the University of Arkansas Honors College for providing me a grant to explore my interests and opening up many doors that I could previously only dream of.