Rafael Gomez-Amaro (rgomezam@ucsd.edu)

Graduate Program:  Biomedical Sciences
Lab PI: Sylvia Evans
Undergraduate Institution: UCLA
Clinical training area in Med-into-Grad: Hematology/Onocology
Main clinical mentors: Catriona Jamieson, cjamieson@ucsd.edu

Quote: “I was surprised how common molecular genetic methods are used in the diagnostics and therapeutics of hematological malignancies. Use of quantitative PCR for determination of minimal residual disease, essentially to detect if the cancer is still present when not detected by traditional flow cytometry or biopsy, is common. State of the art diagnostics and therapeutics in hematology include molecular biology, advance imaging techniques (PET, CT), and intracellular flow cytometry for detection of transcription factors or signaling pathway activation. However, there still exist many unmet needs in diagnostics and therapeutics. Cancer is considered a disease of the elderly; therefore, it is disheartening that many of the successful treatment regimens in hematology, most notably bone marrow transplantation, are not generally considered safe or appropriate for persons over 70. This is one major research area that needs to be addressed nationwide.”

Rational for Med-into-Grad training:  My thesis research is focused on understanding the influence of calcium in early T cell development. I have found that disrupting calcium release in lymphocytes impairs early T cell progenitor survival and differentiation through pre-T cell receptor and calcineurin-NFAT dependent and independent mechanisms. I have also found that the loss of calcium release channels in T lymphocytes leads to the rapid development of acute lymphoblastic lymphoma. While my training in genetics and molecular biology provide a strong foundation for a career in cancer research, I felt my understanding of cancer as a human disease was at best inadequate. As a scientist, I want my research to have the greatest possible impact on the understanding and treatment of human disease. It is my belief that without exposure to the clinical realm, the research questions I investigate now and in the future while interesting from a scientific viewpoint may be completely irrelevant to how cancer is diagnosed and treated. The Med-into-Grad program offered to me the exposure to clinical medicine and patient care that I felt all scientists should experience.

Medical training and identification of medically-relevant research issues: My clinical training is focused on hematology and oncology at the UCSD Moores Cancer Center. The majority of my time was split between two types of activities, clinical case conferences and shadowing physicians in the clinic. In the clinic, shadowing a physician involved directly speaking and listening to cancer patients while discussing their treatment options and progress. The case conferences were directly related to patient care and diagnosis, and allowed me the opportunity to regularly interact with oncologists in a collegial and academic setting for hours at a time. While these activities did not directly involve patient interaction, they were my first exposure to clinical practices in oncology and I found them to be extraordinarily helpful throughout my time in the clinic. Two conferences were important to my experience in Med-into-Grad. The weekly bone marrow transplant case conference often involved intense academic discussion among clinicians about individual patient care as the limits of clinical medicine were reached. It served as a constant reminder that limited treatment options exist after a patient relapses or does not respond to treatment, the so-called salvage therapies, and there is still a great need to answer seemingly simple and easily achievable questions relating to cancer treatment. I also attended a daily hematopathology conference where I learned a great deal more about the methods for diagnosis and staging of hematological malignancies. It was enlightening to do this while I was involved in patient care activities because not only did I see the affects of cancer and treatment on the physical condition of a patient, but I was able to follow the histological changes that occurred. From this standpoint, I have learned much about human hematology both in steady-state and during specific diseases.

Potential Research collaborations:  One research question I found was important was the need to increase stem cell yields for bone marrow transplantation in patients that do not respond well to current mobilization strategies. Limited options exist for patients that cannot generate enough stem cells for successful engraftment. Interestingly, research has come out showing that humans have more blood stem cells in the blood at night. I have spoken with a number of transplant specialists who agree this area deserves attention as a simple adjustment of the time when stem cells are harvested potentially can increase the number of stem cells collected. While I do not plan to address this question in my own research, it can quickly be accomplished through collaboration between with a clinical lab.

Training in diagnostics & therapeutics, and identification of unmet diagnostic & therapeutic needs:  I feel that I have a better understanding of the diagnostics and therapeutics used in hematology and oncology, given the diversity of the field and limited time I have spent in the clinical environment. In hematology, unlike many other disciplines, access to cancerous cells can be relatively simple and many times involves only a simple blood draw such that sample availability is not a limiting feature for diagnosis. While staging often involves biopsy and other surgical procedures, there is less risk inherent to diagnosis and staging in hematology than in other disciplines. I was surprised how common molecular genetic methods are used in the diagnostics and therapeutics of hematological malignancies. Use of quantitative PCR for determination of minimal residual disease, essentially to detect if the cancer is still present when not detected by traditional flow cytometry or biopsy, is common. State of the art diagnostics and therapeutics in hematology include molecular biology, advance imaging techniques (PET, CT), and intracellular flow cytometry for detection of transcription factors or signaling pathway activation. However, there still exist many unmet needs in diagnostics and therapeutics. Cancer is considered a disease of the elderly; therefore, it is disheartening that many of the successful treatment regimens in hematology, most notably bone marrow transplantation, are not generally considered safe or appropriate for persons over 70. This is one major research area that needs to be addressed nationwide. A first step could be as simple as getting all insurance providers to agree on a rationale set age to limit transplants based on the primary literature. The current age limit varies between 60 and 70, and for many malignancies transplant is the only curative or even life-extending option. Two persons of the same age with the same diagnosis should receive the best treatment option available regardless of the insurance provider.  

Diagnostic & Therapeutic collaborations:  I am most interested in finding notch signaling inhibitors that do not have severe GI side effects like the gamma-secretase inhibitors currently used for treating T cell lymphomas do. I plan to develop this idea in the near future.

Long term impact:  The training I received in Med-into-Grad has changed my perspective as a researcher. I feel comfortable reading medical literature relevant to my research and energized and more focused on identifying questions directly related to my own research that can have real clinical implications. I have developed connections with physicians, scientists and non-scientists, whose input I am glad to solicit and who are happy to give it in the hopes that my research helps them someday in the clinic. 

Student-specific experiences:  I believe that my training has allowed me to gain a deeper understanding of cancer, not in the abstract or in comfortable biological terms but as a part of the human condition. People cope with devastating diseases, and seeing this in person and trying to understand their experience is something every researcher should do. My time at the cancer center was not just seeing the pain and suffering of cancer treatment, there are many wonderful things that happen there and I was glad to be able to witness it.

Advice for new trainees--Autumn preparatory quarter:  I would suggest taking histology and getting involved in pre-clinical activities as soon as possible. The clinical case conferences were most helpful to me. Also, contact your clinical advisor as soon as possible, well before you start the winter quarter to make sure your training is set in place and you know where to go on day 1.

Advice for new trainees—Winter clinical training quarter:  I would suggest to listen carefully to what you are being told and don't be afraid to ask questions if you are being overwhelmed. Introduce yourself and be courteous with your requests as clinicians are busy people. I found that just doing that much, every clinician I interacted with was always happy to make time to speak with me on just about anything, from clinical basics to specific treatments of rare diseases to the best sandwich on the cafeteria menu.

Take home perspective on Med-into-Grad at UCSD:  The Med-into-Grad training opportunity is great, but in the end it is really what you make of it. I would definitely recommend this program to other student's, it is a great opportunity to better understand what you are researching and make new contacts as you progress through your career. In all likelihood, most graduate students will never be exposed to clinical scientists and physicians like the ones you meet in Med-into-Grad.