Amanda White (amandatwhite@gmail.com)

Graduate Program:  Biomedical Sciences
Lab PI: Dr. Anne Murphy
Undergraduate Institution: The College of New Jersey
Med-into-Grad Clinical training area: Diabetes
Main clinical mentor:
Dr. Sunder Mudaliar  Sunder.Mudaliar@va.gov

Quote:   “My Med-Into-Grad experience was balanced between clinical observation and participation in clinical research efforts.  My clinical training consisted of attending outpatient clinics in diabetes, obesity and endocrinology, attending post-clinic conferences, endocrinology grand rounds and didactic lectures.  The activities that had the most impact on me were the post-clinic conferences where the fellows and attendings would present and discuss difficult cases.  It was interesting to see how they approached challenging cases and this is where I realized the differences in thought process between clinical and research settings. My clinical research training also included the analysis of data from the various diagnostic tests and the discussion of the results with my clinical mentor gave me insight into how experimental drugs affect glucose homeostasis.”

Rational for Med-into-Grad training:
My thesis project focuses on identifying a mitochondrial mechanism of action of thiazolidinediones (TZDs), which are insulin sensitizing agents used in the treatment of type 2 diabetes.  These compounds possess significant undesirable side effects that limit their clinical utility and are known to occur through binding to the PPAR family of nuclear receptors.  Thus medicinal chemistry efforts by our collaborators have produced PPAR-sparing, insulin sensitizing compounds that we hypothesize have a mitochondrial mechanism of action.   Identification of the exact effects of these compounds on mitochondria and elucidation of the function of potential TZD-binding mitochondrial proteins is required for further successful compound optimization.
     I was interested in Med-into-Grad because I think it is important that we remind ourselves of the big picture in our scientific fields.  Though our graduate work may be very focused on particular molecular mechanisms, the ultimate goal is to impact human disease.  I felt that by observing clinical practices in the treatment of diabetes and obesity, I could glean valuable knowledge about the beneficial effects of current treatments on patients’ lives as well as an understanding of the adverse effects that demand a need for better therapeutics.
     I selected the Diabetes/Obesity training program because it most closely relates to my current research and is an area I have been active in throughout my scientific career.  The TZDs are currently used to treat patients with type 2 diabetes so I hoped that I would be able to see first-hand the benefits and limitations of these drugs.  In addition, my past research experience was in the metabolic disorders field where I performed indirect calorimetry on mice to determine the effects of various compounds on metabolism and glucose tolerance.  The metabolic program at the VA currently has a study underway that involves indirect calorimetry in humans and I was interested in observing this process and comparing the techniques used here to those I had used previously. 

Medical training and identification of medically-relevant research issues: 
My Med-Into-Grad experience was balanced between clinical observation and participation in clinical research efforts.  My clinical training consisted of attending outpatient clinics in diabetes, obesity and endocrinology, attending post-clinic conferences, endocrinology grand rounds and didactic lectures.  Through the observation of doctor-patient interactions I was able to see the practice of medicine from multiple perspectives.  The activities that had the most impact on me were the post-clinic conferences where the fellows and attendings would present and discuss difficult cases.  It was interesting to see how they approached challenging cases and this is where I realized the differences in thought process between clinical and research settings.  I was fortunate that my clinical mentor was participating in several research studies.  I discussed with him how participants were chosen and was able to directly observe the various diagnostic tests as they were being performed.  My clinical research training also included the analysis of data from the various diagnostic tests and the discussion of the results with my clinical mentor gave me insight into how experimental drugs affect glucose homeostasis.

Potential Research collaborations:
I am currently collaborating with Dr. Pam Taub and Dr. Ted Ciaraldi to determine the effects of epicatechin, a component of dark chocolate, on mitochondrial function.  The clinical study consists of twelve weeks of treatment with epicatechin in diabetic and nondiabetic subjects.  Muscle biopsies are obtained and cultured from myoblasts into myotubes.  We then analyze the mitochondria from these cells with the use of functional assays for oxygen consumption to assess their quality and electron microscopy to assess the quantity of and morphology of mitochondria present.  Due to my Med-Into-Grad experience, I may begin a collaboration with Dr. Karen Herbst to determine the effects of doxycycline treatment on skeletal muscle mitochondria in diabetic patients.

Training in diagnostics & therapeutics, and identification of unmet diagnostic & therapeutic needs:
Dr. Steve Edelman discussed with us the current devices for glucose monitoring.  A major limitation in diabetes care is the fact that many patients do not measure their blood glucose as often as would be diagnostically helpful because they do not like to stick their fingers multiple times a day.  Coming down the pipeline are devices that can measure blood glucose through the skin without having to do a finger prick.  In addition, many patients do not take their insulin as prescribed, either because they don’t like injecting themselves or they don’t like to carry the insulin and needles around with them when they leave the house.  Dr. Edelman encourages the use of insulin-injecting pens that are easier to carry and use. 

Diagnostic & Therapeutic collaborations:
Though I do not currently have any collaborations for the future development of diagnostic or therapeutic devices, I will continue to keep up with the technical developments in the field.

Long term impact: 
This experience has encouraged me to continue to perform my research with clinical outcomes in mind.  I think this experience will lead me to pursue more collaborations with clinical researchers.

Student-specific experiences:
After sitting in with patients with diabetes and obesity it became clear that nutrition and exercise are instrumental in the prevention and treatment of metabolic diseases.  Besides observing the fellows in the outpatient clinics, I was able to sit in with the nutritionist where it was constantly reinforced that the “best medicine” for metabolic disorders consists of lifestyle changes such as diet and exercise.  Since this experience I have made an effort to eat a bit healthier and exercise a lot more.

Advice for new trainees--Autumn preparatory quarter:
I strongly recommend reviewing relevant chapters in the textbooks that are provided before beginning the clinical experience.  Of particular importance is a knowledge of the drugs that are used in the field (i.e. classes of drugs, mechanisms of action, adverse effects).  Knowing both the drug name and the common name is essential for understanding conversations between doctors and patients as well as those among the clinical staff at post-clinic conferences.

Advice for new trainees—Winter clinical training quarter:
When you are first getting started, I recommend asking the clinical mentors to suggest papers for you to read that you can then discuss with them.  After a few weeks, when you have a feel for the research in the field, begin to choose papers that you feel are relevant and approach your clinical mentors with questions.  Try a mixture of clinical and basic science papers so that you can learn from each other.

Take home perspective on Med-into-Grad at UCSD: 
Overall this experience was everything I expected and more.  It was great to see medicine from both the perspective of the patient and the health care provider.  The clinical mentors made themselves available to questions and scientific discussions and this really enriched the experience.  I do and will continue to recommend this program to other students.