Ada Shao (adashao@ucsd.edu)

Graduate Program:  Biomedical Sciences
Lab PI: Dr. Miles Wilkinson
Undergraduate Institution: UC Berkeley
Med-into-Grad Clinical training area: Neurologic Diseases
Main clinical mentor:
Dr. Rafii   mrafii@ucsd.edu
Dr. Ravits  jravits@ucsd.edu
Dr. Lessig  Stephanie.Lessig@va.gov

Quote:   “Going into Med-into-Grad, I had expected to enjoy seeing how our work as scientists is applied clinically and also in spending time with patients. I had not expected to come to really prize the time with patients, in hearing their stories, in observing the families’ sacrificial love and care, and though I could never fully understand what they endure, empathizing as much as I could with their situations. Working in the clinic showed me where research efforts are currently lacking and also where knowledge from basic science research could be applied to tangible treatment and prevention strategies for patients. My experiences in the clinic have convinced me to pursue research that is directly applicable to the clinic. I had previously carried the mindset that even the most basic science research is beneficial to humanity, which is true, but after spending time in the clinic, I recognized the urgency with which we should be pursuing research that can impact lives now, rather than decades down the line. The need is great and as the patients and doctors have made clear, they need us as scientists to make those discoveries on their behalf. It was so inspiring to have patients and doctors alike enthusiastically encourage me to pursue research that would benefit those suffering from these diseases."

Rational for Med-into-Grad training:
     MicroRNAs and Nonsense-Mediated mRNA Decay (NMD) are post-transcriptional RNA repression pathways functioning to regulate gene expression and as such play critical roles in nervous system development, function, and disease. Misregulation of these pathways can give rise to a wide range of nervous system diseases, including brain tumors, neurodevelopmental disorders, and neurodegeneration. The goal of my thesis research is to understand how microRNA regulation of NMD functions in neural development/function and how the misregulation of these pathways causes neurologic disease.
     I was interested in Med-into-Grad because it offered the opportunity to better understand the current state of neurologic disease research and treatment and insight into disease diagnosis, progression and treatment. Participating in the Med-into-Grad program would provide much-needed perspective not only on where research efforts are currently lacking but also on how knowledge from basic science research is applied to tangible treatment and prevention strategies for patients. Furthermore, I was excited to interact with and understand the struggles of the people who rely on the discoveries we make in the lab and whom I hope to help through my research.

Medical training and identification of medically-relevant research issues: 
My Fall Quarter clinical training consisted of attending brain-cutting conferences and Neurology Grand Rounds. Beginning in Winter quarter, I attended various Neurodegenerative, Neuromuscular, and Neurodevelopmental Disease clinics, primarily at Perlman, Hillcrest, and Rady’s Children Hospitals. I learned through my experience in the clinic that treating disease is not as straightforward as I had previously thought given the huge variation in disease presentation and in how patients respond so differently to the same treatments. Furthermore, I learned that medications used to treat neurologic disease generally only ameliorate symptoms, having little or no effect on the underlying cause of the disease. For diseases that progress in severity, I realized the need to develop treatments targeted at the underlying mechanism to slow or stop progression, which necessitates a better understanding of disease pathogenesis and affected genes. This, however, is not the case for diseases that stay relatively stable. As an example, autistic children and their families would benefit more from therapies that improve the symptoms than the identification of yet another gene involved in autism.

Potential Research collaborations:
My experience in the ALS clinic particularly impacted my desire to uncover the underlying mechanism of and potential treatments for this disease. I observed huge variation in disease presentation and progression and am therefore especially interested in examining the mechanism accounting for this variability. Recently, mutations in the transcription factor TDP-43 have been identified as factors in the development of ALS. TDP-43 levels are regulated by the Nonsense-Mediated mRNA Decay pathway and by microRNAs, which are the focus of my thesis work. During my clinical rotation, I worked with Dr. Ravits, who specializes in the care of ALS patients and is interested in studying the mechanism of ALS progression. Furthermore, he has amassed a collection of spinal cord samples from ALS patients, with which we could study microRNA and gene expression levels. While no formal collaboration has been arranged, we are discussing potentially exploring collaboration between our laboratories.

Training in diagnostics & therapeutics, and identification of unmet diagnostic & therapeutic needs:
Through my clinical experience, I obtained a working understanding of diagnostic tools and therapies used to treat patients. Diagnosis of neurodegenerative disease is based primarily on symptoms and memory/cognition testing, verified with volumetric MRIs. Neuromuscular disorders are diagnosed by physical exams testing for bradykinesia, rigidity, and reflexes; EMG testing for nerve conduction is used to examine nerve conduction in muscles that may be affected. Despite scoring scales, the tests administered in the clinic can be highly subjective and the results dependent on the condition of the patient on any given day. These tests, therefore, seem error prone but form the basis of diagnosing and tracking progression of these diseases. An area that needs further development in the diagnosis of neurologic disease is identifying quantifiable and easily assayed biomarkers.

Diagnostic & Therapeutic collaborations:
Given the subjective nature of memory and physical exams, it would be useful to develop tools to measure molecular markers of disease. This would be useful both for early diagnosis and for tracking disease progression. The development of such tools is something that clinicians are eager to see developed by scientists in the laboratory, but I did not establish any collaborations to pursue this area of research.

Long term impact: 
Participating in Med-into-Grad gave me a much-needed perspective on the purpose behind conducting biomedical research. Going into biomedical research, I sought to address unmet medical needs, whether by directly studying prevention and therapeutics or by unraveling disease mechanisms and pathogenesis. Working in the clinic showed me where research efforts are currently lacking and also where knowledge from basic science research could be applied to tangible treatment and prevention strategies for patients. Working in the lab, it is easy to get caught up in the daily grind of benchwork and lose sight of the bigger picture. Interacting with patients whom I hope to serve through my research and putting a face to the people who rely on the discoveries we make in the lab has contributed significantly to my desire to address medically relevant and necessary research.

Student-specific experiences:
Going into Med-into-Grad, I had expected to enjoy seeing how our work as scientists is applied clinically and also in spending time with patients. I had not expected to come to really prize the time with patients, in hearing their stories, in observing the families’ sacrificial love and care, and though I could never fully understand what they endure, empathizing as much as I could with their situations. My experiences in the clinic have convinced me to pursue research that is directly applicable to the clinic. I had previously carried the mindset that even the most basic science research is beneficial to humanity, which is true, but after spending time in the clinic, I recognized the urgency with which we should be pursuing research that can impact lives now, rather than decades down the line. The need is great and as the patients and doctors have made clear, they need us as scientists to make those discoveries on their behalf. It was so inspiring to have patients and doctors alike enthusiastically encourage me to pursue research that would benefit those suffering from these diseases.

Advice for new trainees--Autumn preparatory quarter:
I felt that the brain-cutting conferences were useful, especially given my minimal background in neuroscience. The doctors and fellows were very good in explaining the functional anatomy of the brain. It was useful also to see live what the brain looks like grossly and microscopically when affected by particular diseases. If you ask the fellows or doctors, they would likely be more than happy to have you not only attend the brain-cutting conferences but also sit in when they analyze the fixed and stained samples for pathology microscopically. Of course, it is always helpful to brush up on and review anatomy using the textbooks so you can better understand what the doctors/fellows are discussing.

Advice for new trainees—Winter clinical training quarter:
In my experience, I was fortunate to work with clinicians who very readily welcomed me into their groups. It is helpful to have a working knowledge of the current state of the disease field to facilitate discussions and improve understanding. Other than that, like most other people, clinicians and their patients probably enjoy working with students who are enthusiastic and eager and cheerful. I think the patients particularly appreciate a warm smile and thankfulness on our part as students for the opportunity to learn from them.

Take home perspective on Med-into-Grad at UCSD: 
I would enthusiastically recommend the Med-into-Grad program to any student interested in biomedical research. Aside from gaining insight into how our research translates into the clinic, the experience greatly affected my perspective on the urgency and our responsibility to address unmet medical needs in our research. I look back fondly on the opportunities to interact with patients and their families, hearing their stories and putting a face to the descriptions we read in books and papers.