I am an Assistant Professor in the Department of Radiation Oncology. I lead a translational research laboratory aiming to improve cancer patient outcomes. A major component of my research program is to (1) develop strategies for improving the therapeutic ratio of radiation therapy by increasing tumor sensitivity to radiation and limiting normal tissue toxicity and (2) understand the biological mechanisms of treatment resistance. I have received NIH K22 funding to study the role of a biomarker in treatment resistance. I also have/had funding from the Lung Cancer Research Foundation and Elsa Pardee Foundation.
The research projects that are currently being actively pursued in the lab include the following:

Project 1. Cancer-targeting antibody-drug conjugates
Radiation-sensitizing chemotherapy has shown promise in the clinic for cancer treatment. However, toxic side effects limit higher doses of systemically administered chemotherapy. In this project, radiation-sensitizing chemotherapy is delivered specifically to cancer using antibody-drug conjugates (ADCs). We discovered a new cancer antigen that carries the ADCs specifically into cancer cells. Once the ADC is within the cell, the radiation-sensitizing drug is released and enhances the efficacy of therapy. Therefore, this approach delivers radiosensitizing drugs specifically to cancer each day compared to the current once-weekly administration of systemic chemotherapy. This new paradigm of guided delivery of the ADCs to tumors treated with radiation therapy will lead to clinical trials.

Project 2. Role of midkine in lung cancer
Non-small cell lung cancer (NSCLC) ranks among the highest cancer-related mortalities worldwide. Molecular targeted therapy is a growing topic of investigation to improve therapeutic efficacy for NSCLC. A few targeted therapies that exploit aberrant protein expression profiles have been approved for NSCLC. However, the marginal percentage of cancers with improved efficacy observed with these therapeutic approaches highlights the need to discover additional molecular targets. We propose targeting the scaffold protein TIP1, a novel target for lung cancer as identified by analysis of the cancer genome atlas datasets and NSCLC tumor tissue microarrays. The functional domain of TIP1 (PDZ domain) caps the C-terminus of many different cellular proteins that regulate important cellular functions. Knocking down TIP1 revealed that it plays an essential role in cell signaling, cancer development, and progression, making it an attractive target for anticancer therapeutics. Comparing antibodies targeting different epitopes of TIP1, it was found that antibodies against the PDZ domain of TIP1 were most effective in inducing direct cytotoxicity of lung cancer cells but not normal cells. Anti-PDZ/TIP1 antibodies injected into mice bearing lung cancer bind specifically to cancer cells and substantially enhance tumor control. Quantitative mass spectrometry identified Midkine (MDK) as a putative protein that modulates this cytotoxicity by anti-PDZ/TIP1 antibodies. Additional studies suggested that the β-catenin/Wnt signaling may be involved in this up-regulation of MDK after blocking TIP1. Together, these studies led to the central hypothesis that the anti-PDZ/TIP1 antibody upregulates MDK via the β-catenin/Wnt signaling pathway, subsequently modulating downstream cell death mechanisms. In this project, we will elucidate the mechanisms of induction of MDK following the blockade of the PDZ domain of TIP1. In addition, we will evaluate the efficacy of blocking the TIP1 function while simultaneously blocking the MDK function in mouse models of NSCLC.

Project 3. Intercellular signaling by metalloproteases regulating cell viability and resistance to therapies.
A disintegrin and metalloprotease (ADAM) family of proteases induce ectodomain cleavage and shedding of cell surface proteins that regulate cell viability pathways. Overexpression of ADAM10 is correlated with poor survival in lung cancer patients. One of the signaling pathways regulated by ADAM proteases is Eph receptor/ligand complexes on the cell surface. We found cell surface interaction of ADAM10 and EphB3 with a cell surface chaperone protein, TIP1. TIP1 is a targetable cell surface protein that can deliver cytotoxic cancer therapies. Antibodies to the functional domain of TIP1 activate the endocytosis of antibody-drug conjugates (ADCs), and the cytotoxic payload dissociates from the antibody following endocytosis. Blocking the functional domain of TIP1 activates ADAM10 and dephosphorylates EphB3. We hypothesize that TIP1 sheaths the proteolytic activity of ADAM10 on the cell surface, and blocking TIP1 function activates endocytosis via disruption of the Eph receptor pathway. This work will provide new insights into how TIP1 regulates ADAM10/Eph signaling. These studies will provide foundational knowledge toward our long-term goal of developing improved therapies for cancer treatment and an enhanced understanding of the fundamental processes of cancer progression. 

• Lab Website

I enjoy teaching and mentoring students, trainees, and postdoctoral fellows. I have a successful track record of mentoring many students and trainees. I am mentoring two postdoctoral fellows, three students, and two research technicians with different career aspirations in my lab. I am also teaching Radiation Oncology and Nuclear Medicine residents and Cancer Biology Ph.D. students on topics like targeted cancer therapies and mechanisms of cell death. I have led Discussion Sections for the DBBS Molecular and Cell Biology program for the last two years.

My mentoring philosophy is based on the understanding that each mentee may have different career goals and aspirations. I will tailor my mentoring style to ensure each mentee's successful personal and professional development. This requires me to know my students (or early career scientists such as postdocs) and understand their goals. Conversely, I allow my students to get to know me so that I can act as a valuable and inspiring role model. To support the mentee’s development as a scientist, I will help them learn to define a solvable problem, including a testable hypothesis and a way to gather the evidence to conduct the test. To inspire such creativity, my feedback to the student will be in the form of questions that help narrow and focus the topic. By using questions, the mentees defend or alter their approach, implicitly taking responsibility for it and developing independence. By developing their research strategy, I will reinforce the value of their insights. This framework will be formalized by maintaining a laboratory notebook that constantly evaluates a working hypothesis. This continuous re-evaluation acknowledges that only some things we try in the lab works, and mistakes are a part of learning. Acknowledging those mistakes and correcting them promotes scientific integrity and resilience.

A key goal of my mentoring is to foster the confidence that allows a particular student to develop informed, defensible opinions that are the basis of independent thinking that can result in new solutions. Thus, I attentively listen to the students without interruption. This initiates a discussion that identifies unresolved questions and overlooked issues and offers resources. Such a dialogue values the students and preserves their creativity and exploration of new, possibly incomplete, ideas common to students at the cusp of discovery. In the end, enthusiasm for the discussion and respectful exchange enable the research to continue.

Values of integrity, hard work, intellectual curiosity, sharing knowledge, and helping other team members are integral to the success of not only the individual student but also other members of the research team. I strongly emphasize that personal integrity in research is the one invariant that I will not compromise on, which my students take with them as they go on in their careers. I also emphasize that learning is a shared endeavor; the more they share with their lab mates and colleagues, the more they are likely to learn. My students have developed as strong scientists by helping others with their projects and mentoring students who have come into the group after them.

My mentoring philosophy emphasizes helping the student develop a framework of skills, knowledge, and confidence that enable them to pursue their chosen interests successfully. Through project work, they gain practical experience applying their developing skills – they learn best by doing. I expect to learn something new from them, just as they learn from me. I hope that we both grow as scientists from working together.