Amy Hsieh (ahsieh@ucsd.edu)

Graduate Program:  Bioengineering
Lab PI: Dr. Andrew McCulloch, Dr. Michael Berns, and Dr. Robert Ross
Undergraduate Education: University of California, San Diego
Med-into-Grad clinical training area: Cardiovascular Diseases
Main clinical mentors: (Name(s) and email addresses):
Dr. Kirk Knowlton        kknowlton@ucsd.edu
Dr. Sotirios Tsimikas stsimikas@ucsd.edu

Quote:  “MIG provided me a chance to combine my background with a clinical experience to pave the pathway which may lead to the development of novel therapeutics, devices, and diagnostics, and contribute to helping patients have a better quality of life.  I am collaborating with UCSD physicians to improve devices I developed during MIG training, which are now under evaluation for patents.”

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: Surrounding the cardiomyocyte is the extracellular matrix (ECM), which is bridged to the actin cytoskeleton by integrins, talin, and vinculin. The interaction of the extracellular matrix with integrins helps to maintain the structural integrity of the cell and play a key role in mechanotransduction, where mechanical signals cause a change in cell signaling. Current research has indicated that the disruption of proteins involved in these properties can lead to cardiomyopathies and arrhythmias. The long-term objective of my thesis research is to understand the mechanism of how defects in cell-cell and cell-ECM interactions lead to cardiomyopathies. The focus of my research is to study the functional roles of vinculin, its splice-variant, metavinculin, and talin in this process. Using fluorescence resonance energy transfer-based biosensors and an optical trap to locally apply forces, I will evaluate the role of vinculin and talin in isolated cardiomyocytes. This research will allow a deeper investigation of the functional roles of vinculin, metavinculin, talin-1, and talin-2 in integrin signaling, cardiac myocyte function, and provide information about their roles in cardiomyopathies.

The Med-into-Grad is a great program that provides graduate students the ability to look at a specific clinical training area. As a graduate student in Bioengineering, I am driven to seek solutions to molecular mechanisms through the understanding and integration of both biological and engineering principles. In my undergraduate study, I majored in Bioengineering with a pre-medical emphasis and studied post-myocardial infarction healing and remodeling of the left ventricle in mice. Because of my exposure to studying post-myocardial infarction healing and remodeling, I became very interested in cardiovascular diseases. As a result, for my graduate study, I am studying signaling pathways implicated in cardiomyopathies. Although I am passionate about the areas of research that I have chosen, I was eager to learn more about the pathologies of cardiovascular diseases, the current clinical treatments, and was interested to think about how I could form a bridge between my research and clinical applications. I felt that with my current background and proposed graduate research in combination with the Med-into-Grad training, I would have a solid foundation of knowledge that will aid me in my future research. I was interested in participating in the Med-into-Grad program because it provided me with the opportunity to gain a better understanding of the pathologies of cardiovascular diseases and to develop new ideas that will drive future research discoveries and possible therapeutics.

Medical training and identification of medically-relevant research issues: The various aspects of clinical training that I was involved with included: rounding with attending physicians, cardiology fellows, and medical residents, attending discussions about the latest treatments for cardiovascular diseases, observing how and why various diagnostic examinations were performed, and learning about when, why, and at what dose medicinal therapeutics are administered. During my clinical experience, I also learned about how various cardiovascular diseases were diagnosed, how different heart failure cases were treated, and was exposed to how the latest drugs were incorporated in clinical trials. Throughout my clinical experience, I was able to interact with not only the doctors and hospital staff, but also the patients. In observing how physicians treated the diseases and illnesses of patients, I also noted how the patients felt, their symptoms, and noted how the different diseases progressed over a period of time. After being exposed to various activities within the hospital and attending the seminars and discussions, I began to identify medically-relevant research issues that could be addressed. I discovered that there were certain research issues that could be addressed by individuals with a bioengineering background, and after sharing these ideas with various attending physicians, I began to discover additional research areas that I would like to pursue as a result of my clinical training.

Training in diagnostics & therapeutics, and identification of unmet diagnostic & therapeutic needs: During my clinical experience, I was exposed to various diagnostics and therapeutics currently used in cardiology. In brief, several of the state of the art diagnostics and therapeutics include medicinal therapeutics, imaging (i.e. ultrasound, x-ray, MRI), use of cardiac markers, electrocardiography, cardiac ablation, cardioversions, angiography, and angioplasty. 
Although there are a variety of therapeutics and diagnostics available to understand and treat cardiovascular diseases, several of the unmet needs in cardiology that I noted include: therapeutics for idiopathic cardiomyopathies, shifting diagnostics and therapeutics from invasive to non-invasive techniques, and translational diagnostics and therapeutics between the United States and third world countries. Other unmet needs include taking the latest cardiac markers that have been noted in basic research and incorporating diagnostics for those markers in the clinical setting.
Several of the major problems that make the development of better diagnostics and better therapeutics are the difficulty of translating between the clinical setting and basic research. For example, identifying needs found in the clinical environment and designing basic research experiments to meet those needs. Other difficulties include the ability to recreate conditions found clinically in animal models, which would provide a means in which basic research and clinical research could be brought together.

Diagnostic, therapeutic, and research collaborations:  During my clinical experience I had several ideas for new devices.  My ideas were the result of combining my bioengineering background with my Med-into-Grad clinical experience.  I discussed these ideas with various attending physicians including Dr. Kirk Knowlton, Dr. Blanchard, and Dr. Ben-Yehuda.  The specific details of my proposed devices are currently being evaluated for patent protection, and I have plans to collaborate in their development with the physicians above and with individuals in the Bioengineering and Biomedical Sciences department.

Student-specific experiences:  The Med-into-Grad program is a wonderful opportunity that encourages you to think outside of the box. I highly encourage anyone who is interested in helping the development of medical devices, diagnostics, and therapeutics to participate in this program. This program will help you develop as a researcher, to understand and explore new pathways, and it encourages you to look at various situations from different perspectives. I believe that this experience has made me a better researcher and has highly impacted my career goals in pursuing disease-oriented research which may lead to the development of devices, diagnostics, and therapeutics.

Long term impact: The Med-into-Grad training has provided insight about the urgency of the need for crosstalk between basic research and clinical medicine. It also exposed me to exploring other types of cardiovascular diseases and looking at how current treatments could be modified to treat a different disease. My clinical experience has encouraged me to look at more overlap between current clinical diagnostic tests and diagnostic tests used in our animal studies, to look at markers that exist in basic research and develop ideas as to how to identify these same markers in the clinical setting accurately and cost effectively.  As a researcher, this program also encourages me to form collaborations between various people, to bounce ideas off each other, for the greater good of helping patients. I also feel that I learned to think about the effects of other systems on my specific system. For example, the cardiovascular system is affected by other systems including renal, respiratory, and endocrine. By keeping these factors in mind, I will be able to develop more specific scientific questions and experimental designs. Overall this training has encouraged me to pursue disease-oriented research in hopes of developing improved or novel medical devices and therapeutics.

Advice for new trainees--autumn preparatory quarter:  To best prepare yourselves for your clinical experience in Winter quarter, I would most highly recommend that you attend the Cardiology Grand Rounds and Cardiovascular Science Series seminars. In addition, I would highly recommend reading Parts I, II, and III of Braunwald’s Heart Disease. These chapters exemplify the importance of the Med-into-Grad program, how clinical research interacts with basic research, and provides background for several different types of diagnostics that trainees will be seeing first hand during Winter quarter.  Some other activities that I would recommend to students is to read the cardiology sections of the internal medicine pocketbooks to help identify the main types of drugs and diagnostics that are used in cardiology and why certain things are done or focused on during the physical examination of the patient.

Advice for new trainees—winter clinical training quarter:  My advice to new trainees is the one that was passed onto me: Take the initiative. Introduce yourself, your interests, your background, and information about the Med-into-Grad program. Talk to the interns, the residents, the fellows, the nurses, and the attending physicians. Although the hospital atmosphere is fast paced and at first the vocabulary may seem to be overwhelming, absorb what you can and take notes. I recommend looking up the answers to your questions in textbooks, on the internet, and when appropriate, ask the individuals around you. To make your experience more fruitful, stay on top of the schedule. Know what the basic schedule of the various different diagnostic examinations or procedures is. If you know when, where, and what is going on different days and times, you will be able to learn more, it will also help to cater your interests because if you are more interested in one specific type of disease, you will know exactly when to join in on a procedure, or a discussion about a case. I would recommend an internal medicine, drug, and abbreviations pocketbook. These are helpful resources which will bring you up to speed on the clinical vocabulary and help you gain a better understanding of why certain medicinal treatments are chosen and for what reasons. For cardiology, I would specifically recommend getting a stethoscope and the heart sounds CD which will teach you how to recognize the difference between a healthy heart and a diseased one.  

Take home perspective on Med-into-Grad at UCSD: My overall opinion of the Med-into-Grad program is that it is a wonderful program which can provide graduate students an opportunity to broaden their overall knowledge of human diseases, diagnostics, and treatments.  It also encourages students to think about research from a disease-oriented point-of-view.  I highly recommend this program to motivated students. I believe that this program will provide those students a chance to take their background in combination with clinical experience, to pave the pathway which may lead to the development of novel therapeutics, devices, and diagnostics, and contribute to helping patients have a better quality of life.