Esmeralda Ruiz (ecruiz@ucsd.edu)

Graduate Program:  Biomedical Sciences
Lab PI: Jing Yang, PhD
Undergraduate Institution: University of California, Irvine
Med-into-Grad Clinical training area: Cancer (Hematology/Oncology)
Main clinical mentor:
Dr. Richard Schwab  rschwab@ucsd.edu
Dr. Barbara Parker  baparker@ucsd.edu

Quote:   “Being a participant in the MIG program has fundamentally changed my perspective as a cancer researcher. I now think much more deliberately about how my research can directly impact the future of oncology and formulate experiments to address important limitations of current cancer therapies. As traditional bench scientists, the clinical world can seem very remote and almost mysterious. We have little to no exposure to clinicians, pathologists and other professionals that see the diseases we study on a daily basis. After meeting and working with numerous physicians and hospital staff, I have become aware of the plethora of resources available to me. It is much easier now to contact someone if I want to obtain tissue samples for a particular cancer or have an idea for a possible new collaboration, or simply have a question about how an observation in the lab might be clinically relevant and vice versa."

Rational for Med-into-Grad training:
My thesis research is exploring the role of Twist1 in regulating cell-cell adhesion to promote Epithelial-Mesenchymal-Transition and cancer metastasis. I wanted to get a better grasp of the disease as it presents itself in the clinic as well as become more familiar with how cancer is currently treated and possible new directions for cancer treatment.

Medical training and identification of medically-relevant research issues: 
I shadowed oncologists as they met with patients in both inpatient and outpatient settings at Thornton Hospital and the Moores Cancer Center, respectively. This gave me a first-hand look at how cancer not only presents itself in the clinic but just as importantly, the current therapies available at various stages of the disease. Although I have been reading cancer research articles throughout my graduate career, it was very eye opening to see patients in the clinic and hospital at various stages of the disease. It gave me a sense of urgency to see patients and doctors who were basically helpless in the face of recurring refractory disease. It was difficult to realize there was nothing more that anyone could do for certain patients after the point where current therapies are no longer effective. Researchers to date have mainly focused on targeting primary tumor growth and invasion. An equally important and maybe more relevant are of research would be to determine how cancer cells become resistant to therapy after relapse.

In addition to inpatient and outpatient rotations, I also attended tumor boards for breast and lung cancer. This gave me insight as to how cancer is diagnosed, staged and how doctors discuss treatment options as well as the rationale behind treatments. One of the most important insights in my clinical training came from attending tumor boards. Although I was already aware that imaging is the main method by which cancer is detected, confirmed or tracked I realized imaging can only provide so much resolution and the tiniest amounts of cancers would not necessarily be detectable by imaging. That allows residual cancer to remain undetected after treatment and leaves the possibility open for relapse. It would be ideal to find novel and more sensitive ways of detecting the presence of any remaining cancer after treatment and possibly extend or change treatment until residual cancer is completely eradicated.

Potential Research collaborations:
I discussed ideas for translational research projects with physicians and the possibility of future collaborations. They were very open to my ideas and also gave me valuable feedback as to their feasibility as well as ongoing research in the field. At the moment however, I did not establish a firm plan to act on the discussions. I will be graduating in the next few months but would like work on the project as a post-doc.

Training in diagnostics & therapeutics, and identification of unmet diagnostic & therapeutic needs:
The field of cancer research and oncology is large, and it can be quite daunting for any student. As a graduate student in the UCSD Biomedical Sciences program, I took classes on a variety of topics concerning the biology of cancer as well as attended numerous seminars and conferences. In these respects, the BMS program helped me to establish a firm foundation as to the current state of cancer research. Unfortunately, the current BMS curriculum does not cover how cancer is diagnosed and treated. This, in my opinion is just as important.

My interactions with doctors and patients made me especially aware of the serious limitations of current cancer treatments. I was a bit disappointed to learn that for decades, traditional cancer therapies have not evolved much. The most widely used treatments such as chemotherapy or radiation shrink or kill tumors by non-selectively targeting fast-dividing cells. This is accomplished mainly through DNA intercalation or inhibition of cell division machinery resulting in high levels of toxicity as normal cells are also killed or damaged. This toxicity, although potent, can be tolerated in strong, otherwise healthy adults but can be problematic or lethal to elderly patients or those already weakened by their disease. In fact, I was witness to a few cases where doctors could not do any more for the patient because the patient was simply too weak to withstand therapy. Additionally, I witnessed patients with long-term and even permanent and seriously debilitating neuropathy caused by their chemotherapy regimens. This drove home the point that it is imperative that we selectively target tumors and largely exclude healthy tissue. Fortunately, there has recently been a shift in the field to more targeted anticancer agents (MTAs). These aim to target factors specifically aberrant in tumors. MTA targets include growth and angiogenic factors, aberrant DNA repair machinery and other deregulated proteins. Given that our ability to efficiently target cancer cells will rest on further identification of factors specific to cancerous growths, I hope to contribute in identification of new targets though further characterization of and delineation of the differences between normal and malignant tissue.

Aside from the toxic effects of many current cancer treatments, I was also witness to the sad reality of disease relapses and drug resistance in patients who appeared to at one point be cured. It is currently not clear how dormant cancer cells escape treatment and re-surface years later more aggressive and lethal. I am interested in dissecting out the molecular differences between aggressive cancer cells that become resistant to therapies and those of the initial tumor to identify new targets for therapy. Furthermore, I am interested in the possibility of future collaborations to identify specific markers circulating in the blood that may uncover the presence of cancer despite escaping detection by conventional imaging. Changing or prolonging treatment if residual disease is detected may help prevent reoccurrences.

Long term impact: 
The “publish or perish” academic life can be grueling and it can sometimes be easy to lose sight of the true goal of discovery. Having now taken a brief part in clinical oncology, I can honestly say it has and will impact my perspective as a cancer researcher. The new perspectives given to me by this experience has helped me to have a deeper and more holistic understanding of the field. I have realized the importance of considering not only how a tumor divides, but how it grows and thrives as well as how its interaction the environment might promote cancer growth and spread. I will keep this in mind as I model the growth and spread of cancer in the lab.

Furthermore, having a more complete understanding of the current state of oncology has allowed me to consider why it might be that certain treatments may not be completely effective and how therapies might be improved or how the current paradigm of treatment can be re-considered.

Student-specific experiences:
The Med-into-Grad program has had a big impact on my daily life as a researcher. Often times, science projects can fail or be stagnant. It can be difficult to remain motivated at times. Having seen and spoken to cancer patients who were told they were terminally ill, I came away with a renewed sense of urgency to do what I can to contribute to the field. On the flip side, seeing patients cry with joy when they were told that they were cured really touched me and gave me hope for the future of cancer therapy.

In addition to clinical rounds, the resources that MIG has provided have been very useful for my training. First and foremost, I opted to take the full histology class taken by students at the school of pharmacology. The class focused on normal tissue histology of the body and has already served me well in my research. I have drawn on this knowledge during mouse autopsies as I inspect tissue for evidence of metastatic disease. Furthermore, during my rotations I had the opportunity to go into the hospital histology core and, along with doctors, inspect histology slides from patient tissue samples. The pathologist elaborated on how various cancers were identified and graded by inspection of these histology samples. I was happy to have sufficient background to understand the pathologist, distinguish samples of various tissue origins and identify areas of neoplastic growth. I was excited to see a slide in which tumor cells were clearly squeezing between the endothelial wall of a blood vessel, either entering systemic circulation or exiting into surrounding tissue. This is a rarity in the laboratory setting, and something I had only read about. To see it in vivo was striking.

Aside from learning about histology, I have been able to purchase textbooks on cancer biology and oncology to assist me during my clinical rotations and my current and future studies. As a student, this would normally be cost-prohibitive. These texts have been an invaluable source providing information such as I how cancer is staged, specific markers used to identify tumor origins, development and use of novel therapies, the history of cancer treatment and much more.

Conferences are an excellent source for meeting new potential collaborators, present our research findings as well as for exchanging ideas or keep abreast of the newest advances in our field. At the very least, they have often served to re-invigorate me and come home with new ideas and perspectives. Unfortunately, due to the large number of staff in our lab, we do not usually have access to funds for travel. Especially not to a conference entirely of our choosing. I greatly appreciate the funds that the MIG program allowed for travel, as I will be using them to attend a cancer conference at Cold Spring Harbor in the next few months.

Advice for new trainees--Autumn preparatory quarter:
Although not required, I recommend taking the full histology course instead of the self-study if you are interested in dermatology or cancer. Histology is not easy and it really helps to attend the lectures and get additional insight as well as help from the TA’s.

Advice for new trainees—Winter clinical training quarter:
I recommend asking as many questions as possible. Doctors welcome questions and it makes them more excited about having you around if you show your interest. I also recommend having something to take notes so you can keep track of patients as well as jot down anything you don’t understand to ask doctors during breaks.

Take home perspective on Med-into-Grad at UCSD: 
If you do cancer research, the Med-into-Grad program is an indispensible part of your training. By exposing you to the clinical and human side of the disease, you will gain a broader perspective for your research. You will learn how cancer is diagnosed, how doctors make decisions on treatment regimens, as well as the limitations of current therapies. This will serve to give you a better foundation for experimental design to better address shortcomings in the current state of oncology. Aside from what you will take from your experience in the clinic, you will also be an asset to doctors who are interested in your area of research and are eager to discuss your findings. Being a participant in the MIG program has fundamentally changed my perspective as a cancer researcher. I now think much more deliberately about how my research can directly impact the future of oncology and formulate experiments to address important limitations of current cancer therapies. As traditional bench scientists, the clinical world can seem very remote and almost mysterious. We have little to no exposure to clinicians, pathologists and other professionals that see the diseases we study on a daily basis. After meeting and working with numerous physicians and hospital staff, I have become aware of the plethora of resources available to me. It is much easier now to contact someone if I want to obtain tissue samples for a particular cancer or have an idea for a possible new collaboration, or simply have a question about how an observation in the lab might be clinically relevant and vice versa. Additionally, being aware of available resources and having them at my disposal helps broaden the scope of any given experiment.