Elyssa Burg (eburg@ucsd.edu)

Graduate Program:  Biomedical Sciences
Lab PI: Jason Yuan
Undergraduate Education: Northwestern University
Med-into-Grad clinical training area: Pulmonary diseases and Critical Care
Main clinical mentors: Judd Landsberg (jlandsberg@ucsd.edu)

Quote: “A major obstacle in developing more or better drugs is simply that pulmonary hypertension lacks a uniform presentation. Some people respond to certain drugs very well, while others fail to respond to all three, and the reason for this is unknown. Until the molecular understanding of the disease is better understood, there will probably always be a subset of patients who cannot be treated by the current medications.“

Rationale for Med-into-Grad training:
Medical training and identification of medically-relevant research issues:
Training in diagnostics & therapeutics, and identification of unmet diagnostic & therapeutic needs:
Diagnostic, therapeutic, and research collaborations:
Student-specific experiences:
Long term impact.:
Advice for new trainees--autumn preparatory quarter:
Advice for new trainees--winter clinical training quarter:
Take home perspective on Med-into-Grad at UCSD:

Rationale for Med-into-Grad training:  My thesis laboratory’s main focus is pulmonary arterial hypertension. Because the genetic contribution to this disease is thought to be complex, information regarding inheritance will likely come from the study of multiple genes. My project specifically focuses on mutations that were found in a voltage gated potassium channel in severe idiopathic pulmonary arterial hypertension patients. I have been studying the electrophysiological and molecular aspects of the mutant channels compared to wildtype channels to elucidate the channel’s structure function relationship as well as to determine whether these mutations could in part be responsible for certain pathological findings of pulmonary arterial hypertension. When I first heard about the Med-into-Grad program, I was immediately interested in participating. I had been exposed to the clinical side of the disease through discussions with medical fellows and clnicians who had worked in the lab, but I felt like I was getting little insights into the disease, rather than the full knowledge. Being able to gain a wider understanding of pulmonary hypertension with hands-on experience in the clinic seemed like a perfect compliment to my research project and the environment in which I was working. Additionally, UCSD is at the forefront of pulmonary hypertension clinical care and is one of the world’s leaders in pulmonary thromboendarterectomy (PTE), a procedure pioneered by UCSD surgeons in the 1970s in the treatment and cure of chronic thromboembolic pulmonary arterial hypertension (CTEPH), a specific type of pulmonary arterial hypertension that is initiated by an unresolved clot in the large pulmonary arteries. I knew that participating in the Med-into-Grad program within UCSD’s Pulmonary and Critical Care division would be an invaluable learning experience.

Medical training and identification of medically-relevant research issues:  The main focus of my training was rotating with the PTE team at Thornton. I was able to participate/shadow every aspect of the care they give to the incoming patients, from meeting and greeting, to presurgical testing (x-ray, echo, angiogram, etc.), to surgery (including bypass, clot removal, etc), to recovery in the ICU and on the wards and postsurgical testing (including V/Q scans, 5 minute walk tests, etc). I also became familiar with reading patient charts and what to look for that was outside the classic textbook presentation of pulmonary hypertension. The single most important insight the training gave me was that there are some CTEPH patients who go in for surgery and post-surgically, they have persistent pulmonary hypertension (probably the result of underlying small vessel disease). These patients have a much higher post-op mortality rate (about 30%) compared to the patients whose pressures and resistances return to normal post-op (~4%). If there were a way to identify the patients who have underlying small vessel disease in the context of CTEPH, then they could be treated for a number of months with drugs that are used to treat non-CTEPH PH patients. After treatment decreased the pulmonary artery pressure/pulmonary vascular resistance, these patients would be more likely to have successful post-op outcomes. Therefore, my research, by contributing to the overall understanding of the possible genetics contributions to idiopathic pulmonary arterial hypertension (small vessel disease), would ultimately be helpful in creating a genetic screen of CTEPH patients to identify those who would benefit from being treated with PH medication before undergoing PTE surgery.

Research collaborations: I participated in the program in the middle of my 4th year of graduate school, so my project was pretty well defined and progressing well by the time I participated in Med-into-Grad. My project also already involved patient samples (the mutations were found in patients whose DNA samples we had taken) and occasional talks/interactions with clinicians in the division. However, I did decide to add my main clinical mentor, Judd Landsberg, to my thesis committee as a result of the interaction I had with him during the program. I felt that as a clinician who had also done research, he was really able to bridge the gap between bench and bedside and that he would be an invaluable asset to my committee.

Long term impact:  The training impacted my perspective as a researcher by widening my understanding of pulmonary hypertension. In subsequent talks and papers/reviews that I wrote, I was able to more comfortably and definitively talk about the potential clinical aspects and impacts of my research. There is not any one specific thing I learned that will change my future actions. Participating in MIG enforced my already existing belief that meaningful research is directly related to some disease. If I were planning on doing a postdoc, I’d probably aim my research at some of the questions that were raised for me in my clinical training (what leads to chronic clot, how does it cause an increase in PVR, how can we detect small vessel disease in the context of CTEPH). Also, in the future I would be more likely to do research in a clinician’s research lab. Through interaction with him or her and other clinicians, I would try to orient my research to be as clinically relevant as possible.

Training in diagnostics & therapeutics, and identification of unmet diagnostic & therapeutic needs:  There are 3 main medications for treating pulmonary hypertension that is not caused by either CTEPH or left heart failure. These include prostacyclin analogs, including inhaled iloprost and intravenouns analogs (these are administered as last resorts (other than lung transplantation), as the patient needs to have a permanent indwelling catheter for drug delivery and carry the medicine with him at all times. Some versions of this medication need to be kept cool, so an ice pack also needs to be maintained with the medication pouch). Endothelin receptor antagonists and phosphodiesterase-V inhibitors (like sildenafil) are also administered orally. However, the problem with treatments is that there is no standardized approaches to treatment and different patients respond very differently to the drugs alone or in various combinations. The patients who don’t respond well to any combination of drugs are generally put on the list for lung transplantation. It seems like a major obstacle in developing more or better drugs is simply that the disease lacks a uniform presentation. Some people respond to certain drugs very well, while others fail to respond to all three, and the reason for this is unknown. Until the molecular understanding of the disease is better understood, there will probably always be a subset of patients who cannot be treated by the current medications. However, this should not be taken to mean that the three existing medications are not effective. They are very effective, and in the last 10 years that they have been developed (as a result of basic research that identified cellular abnormalities in PH patients) and come into widespread use, they have significantly reduced the number of people who have PH who are awaiting lung transplantation and/or dying from untreated PH. Lastly, the average time to diagnosis of PH has been 5 years. Increased awareness among primary care physicians of this disease should help in diagnosing it earlier, and therefore perhaps leading to better treatments.

Advice for new trainees--autumn preparatory quarter:  I think going to the grand rounds and fellows conferences on Thursdays was very useful. I learned a lot about various diseases that the Pulmonary and Critical Care division sees, but I also became familiar with terminology that I would hear a lot during the winter quarter clinical training. I also met the physicians of the division during these conferences. The pathology self study was also very useful in bridging the gap from cellular level research/cellular level understanding of the disease to manifestations of the disease at the level of the patient. Understanding what was going wrong at the tissue/organ level helped me better understand clinical aspects of the disease, more so than only a molecular understanding would have done. Lastly, regular meetings with my clinical mentor during fall quarter were very helpful. He was able to prepare me for what I was going to be learning in the clinical setting as well as directing my independent reading toward the best clinical sources.

Advice for new trainees—winter clinical training quarter:  I think going to the Grand Rounds and introducing yourself there (by way of Patricia Finn) in fall quarter is the best way for physicians to get to know who you are and to expect you in the winter months. Then when you show up on their clinical team, they will know who you are and what you are doing there. Everyone in the division is more than happy to help answer your questions, so ask them! Also, the PCCM division sees a lot more patients other than the PH (and CTEPH) patients. If you are interested in learning more about COPD, asthma, sleep disordered breathing, or intensive care medicine, etc., just ask to be pointed to the right attending whom you can follow.

Take home perspective on Med-into-Grad at UCSD:  I think my MIG training was invaluable to my career as a researcher and a scientist. I would recommend this program to anyone whose research touches on any aspect of any disease. If you can find a clinical group that treats the specific disease you study, great. You will come away with a much better understanding of what you are studying in the lab and how your research findings could be useful to the treatment of the disease. If there is no group who treats the exact disease you study, the training is still great because you will get to become familiar with the clinical setting – what are the priorities there compared to in the research environment, etc.