Rachel Zarndt (rzarndt@ucsd.edu)

Graduate Program:  Biomedical Sciences
Lab PI:  Rolf Bodmer, PhD / co-PI: Gabriel Haddad, MD PhD
Undergraduate Institution:  Willamette University
Med-into-Grad Clinical training area:  Pulmonary Diseases
Main clinical mentor:  Judd Landsberg, MD   jlandsberg@ucsd.edu

Quote:   “Through Med-into-Grad I was introduced to pulmonary research groups with which I will continue active participation through my PhD training in both weekly research meetings and monthly meetings on specific applications to oxygen-related therapies. These cross-pollinations would not have been possible without the clinical training and I am very excited to know my thesis work will have direct translational impacts, if only immediately through regular scientific discussions with clinicians."

Rational for Med-into-Grad training:
I joined Med-into-Grad to obtain experiences that would both broaden and embellish the understanding of my field of interest, hypoxia, from basic science through current clinical treatment options. In the future, I expect to put into practice skills learned at UCSD to benefit the people and populations directly impacted by these insights; either by field research with high altitude sojourners and residents, or through a heightened appreciation of hypoxic pulmonary diseases that affect sea-level populations.

Medical training and identification of medically-relevant research issues: 
Training through this HHMI program was a truly exceptional experience that advanced my specific passion to teach physiology and directly shaped my investigations of the genetic underpinnings of high altitude physiological adaptations to be more translationally relevant. While the pulmonary track was certainly the most relevant to my research interests in hypoxia, the additional clinical exposure I received in cardiovascular medicine was fascinating and directly beneficial to my thesis topic investigating cardiac-specific adaptations.

My day-to-day clinical experiences varied with the nature of the patients that arrived at the ICU. This allowed participation in following treatment plans across a range of diseases; from ALS and end-stage cancer to acute brain injury and pneumothorax. A large portion of the training revolved around following clinicians on morning rounds through various specific clinical areas: The VA ICU, the Thornton ICU, pulmonary hypertension patient rounds, and chronic thromboembolic pulmonary hypertension post-surgical ICU. Post-rounds talks with Dr Landsberg and the clinical fellows helped unravel the more complicated medical mysteries as well as open discussion for emerging treatments or potential research ideas directly relevant to patients we’d seen earlier in the day. One of the most beneficial portions of the training came from discussions of clinical papers I would bring to one-on-one meetings; these talks honed my appreciation for the clinical research related directly to my field of research through the lens of the physiology principles taught clinically.

I also had the opportunity to participate in afternoon outpatient rounds and afternoon procedures, both of which provided personal connection to individual patients. My most memorable experiences came not from novel science discussions, but from personal discussions with patients about their highly individual struggles with disease. The realization that each patient is essentially “n=1” expanded my appreciation for the art and science of medicine, as well as reinforced the idea that even the most finely controlled experiment cannot reproduce the complex physiology occurring in the human clinical setting.

Potential Research collaborations:
While my thesis research aims to understand the Drosophila response to acute, chronic and adapted hypoxia, it is my long standing interest and passion to understand the mechanisms and potential treatments of hypoxic conditions affecting humans. During my thesis work, I’ve had the great opportunity to work directly with three clinical scientists, all pulmonologists, who specialize in high altitude physiology. However, these experiences were all through basic science endeavors and I had yet to obtain first-hand clinical experience with patients suffering from hypoxic illnesses. The Med-into-Grad program allowed time away from research in order to foster a genuine appreciation for the complexities of human disease. Most importantly, Med-into-Grad broke down any remaining hesitance to approach clinicians with questions related either to current medical treatment options, or to ideas for translational research projects. I now feel very comfortable discussing both clinical and basic science questions with clinicians, and know that pursuits for future collaborations will be met with enthusiasm from the clinical side. I’ve initiated discussions to start collaboration with a thoracic surgeon/scientist who fortuitously investigates the same molecular pathway in human lung tissues that I chose for my thesis work in Drosophila.

Training in diagnostics & therapeutics, and identification of unmet diagnostic & therapeutic needs:
Diagnostics in pulmonary medicine seem to rotate around a condensed axis of questions, for example; is the pulmonary disease obstructive or restrictive? Is the lung pathology cardiogenic in origin? Through Med-into-Grad, I’ve been given a toolbox to understand most diseases in the pulmonary field, as well as the impacts of other diseases on pulmonary critical care. While my understanding of disease progression will not rival a clinician’s perspective, I do feel that I can identify areas where research can make improvements. For example, diagnostics between the different types of pulmonary hypertension (PH) depend on the origins of the disease (which can either be surgically mediated, as in the case of chronic thromboembolic pulmonary embolism, or treated pharmacologically, as in pulmonary arterial hypertension). However, the majority of PH is idiopathic and incurable. Treatment plans revolve around controlling symptoms related to the hypoxia induced by constricted pulmonary vasculature, including oxygen therapy. Several generations of drugs exist to treat PH, and I found it interesting that they are often given in order of their historical finding rather than through algorithms based on scientific reasoning.

Diagnostic & Therapeutic collaborations:
I would like to see if PH drugs could be used for treatment of acute hypoxic injuries and disease (for example, acute mountain sickness, which can induce a temporary/reversible form of PH through hypoxic pulmonary vasoconstriction). Application of known PH drugs in this relatively understudied field might have immediately accessible applications. Further, the use of drugs traditionally used in altitude acclimatization may ameliorate the symptoms of PH; this is another understudied topic which I’ve begun collaboration with pulmonologists to investigate further in Drosophila models, potentially using the fly heart as a novel model of pulmonary hypertension.

I also believe the use of oxygen as a therapeutic may have toxic side effects that are not yet fully recognized in the clinical setting, I will study these ideas further by examining clinically relevant “reperfusion” injury and hyperoxia in Drosophila. These are ideas that were directly fostered by Med-into-Grad experiences.

Long term impact: 
While hypoxia is first and foremost a pulmonary condition, it also involves an understanding of cardiovascular and neurological complications. Thus, my long-term goals include uniting my neuroscience and physiology backgrounds with a direct clinical experience to advance an understanding of how the major organ systems of hypoxia (brain, heart and lungs) function under states of chronic or acute hypoxia. Med-into-Grad provided a perfect platform to integrate these disparate disciplines by necessitating the need to think about multiple organ systems simultaneously. Most importantly, communication skills gained in the clinical setting will translate back to benefit the clarity of my research presentations and future plans to teach physiology.

Student-specific experiences:
Through Med-into-Grad I was introduced to pulmonary research groups with which I will continue active participation through my PhD training in both weekly research meetings and monthly meetings on specific applications to oxygen-related therapies. These cross-pollinations would not have been possible without the clinical training and I am very excited to know my thesis work will have direct translational impacts, if only immediately through regular scientific discussions with clinicians.

Interestingly, in addition to the lab/clinic cross-pollination, this training also initiated interesting discussions with members of the public interested in clinical relevancy of specific research areas. It is certainly possible these discussions will lead to future research .

Advice for new trainees--Autumn preparatory quarter:
If possible/relevant, participate in the Block I (first-year) medical school coursework in the fall, which will cover the basic principles of physiology relevant to your organ system. The Block II (second-year) coursework covers pathophysiology of organ systems in detail, but you will probably pick up the details of this during clinical rotations. Participating in these courses requires special permission and you cannot receive course credit, but the courses are very well organized compared to graduate courses (which by nature tend to laser focus only on very novel ideas, ignoring broad medical complexities of physiology).

Advice for new trainees—Winter clinical training quarter:
My best advice is to engage directly with individuals who interact positively with you and encourage your questioning. The fellows are your friends! Don’t be afraid to ask questions or to ask to observe procedures; clinicians want you to interact as much as possible and will talk with you the more you talk with them.

Take home perspective on Med-into-Grad at UCSD: 
I would undoubtedly recommend the Med-into-Grad program to new and seasoned PhD students looking to enrich their academic training. It is truly a unique and invaluable opportunity to learn first-hand how clinicians use our research findings. More importantly, this type of training provides insight that will likely come to full fruition later in one’s research career. I certainly feel Med-into-Grad trained me early my scientific career to become a translational scientist, and that I am now more capable of communicating to a wide audience by distilling my research interests and findings down to a palatable size with clear, useable take-home messages (this is how clinicians communicate so well). In all, this was an invaluable experience that initiates cross-pollination of ideas and generates a renewed enthusiasm to pursue research questions in both their minute detail, as well as translate findings into their broadest applications.