Judith Scheliga (scheliga@burnham.org)

Graduate Program:  Burnham Institute Biomedical Sciences
Lab PI: Dr. Dieter A. Wolf
Undergraduate Institution: University of Regensburg, Germany
Med-into-Grad Clinical training area: Cancer (Hematology/Oncology)

Main clinical mentors (Outpatient Clinics):
Dr. Richard Schwab (Breast Cancer)   rschwab@ucsd.edu
Dr. Fred Millard (Prostate Cancer)   fmillard@ucsd.edu
Dr. Lyudmila Bazhenova (Lung Cancer)   lbazhenova@ucsd.edu
Dr. Benjamin Yu (Dermatology)   byu@ucsd.edu

Main clinical mentors (Inpatient Rounds):
Dr. Barbara Parker  baparker@ucsd.edu
Dr. William Mitchell  wmmitchell@ucsd.edu
Dr. Tony Reid  tonyreid@ucsd.edu
Dr. Stephen B. Howell  showell@ucsd.edu
Dr. Fred Millard  fmillard@ucsd.edu

Quote:   “The knowledge I acquired has definitely influenced the way I can interpret findings that I make while working on my own project. But I am also more capable of putting other cancer research projects into context and to better understand the approaches and potential benefits of these projects. But most importantly, I feel that knowing the clinical side of disease research is something that any scientist should possess! I feel more confident when interacting with non-scientists, because most questions that people ask are of a clinical nature. And I have no doubt that this knowledge will have a huge impact on my career in the field of cancer research."

Rational for Med-into-Grad training:
My Ph.D. dissertation project addresses the involvement of the putative tumor suppressor Int6/eIF3e in mRNA translation and breast cancer. The sequence Int6 encodes the highly conserved e-subunit of the translation initiation factor eIF3, which has been implicated in mammary tumorigenesis, while the underlying mechanism remains unknown. The protein eIF3e has been identified as part of the Translasome, a multi-protein complex containing ribosomal subunits, initiation and elongation factors, as well as proteasome subunits, chaperones, and ubiquitylation enzymes. We hypothesize that the Translasome represents a physical link between the protein synthesis and degradation machineries and that Int6/eIF3e plays a specific role in co-translational quality control through its recruitment of the proteasome to translating ribosomes, which renders it essential under stress conditions that increase the synthesis of misfolded proteins. Specific aims of my project include the detailed characterization of the role of eIF3e in translation, using fission yeast as a model system. Working on a project which involves basic research on a tumor suppressor protein, I was very interested in learning more about the clinical side of my research field, which I am normally not exposed to, and the Med-into-Grad program gave me this unique opportunity.

Medical training and identification of medically-relevant research issues: 
During my MIG training, I participated in inpatient rounds with the Heme/Onc team at Thornton Hospital. I also attended inpatient clinics in breast, lung, and prostate cancer, as well as case conferences and educational lectures for several types of cancers. I learned to identify tumors on CT scans, PET scans, and X-rays, and I was able to observe how physicians interact and communicate with patients in difficult situations. The most important insight I gained was how different types of cancers behave very differently in the human body, and that physicians have very few treatment options in certain cases due to the extreme aggressiveness and fast growth of cancers such as pancreatic cancer or certain types of lung cancers, while other types of cancers such as germ cell tumors usually have very good prognoses even when they have reached extensive sizes and have spread to different organs. This experience helped me to identify research areas where there is a great need for better therapeutics and early detection methods.

Potential Research collaborations:
Most of the physicians I worked with were very willing to discuss research areas where current treatment options or diagnostic tools are very limited, the reasons for these limitations, and potential strategies to overcome them. Furthermore, most of the physicians are actively enrolling their patients in clinical trials whenever possible. Dr. Bazhenova in particular was very interested in keeping in touch with her students to discuss research ideas and unmet needs in the clinic.

Training in diagnostics & therapeutics, and identification of unmet diagnostic & therapeutic needs:
I had the opportunity to learn about chemotherapy regimens, hormonal treatments and radiation treatments that are available for various types of cancers. I also learned about screening tools such as mammograms and the PSA test, as well as diagnostic tests, including CT scans, PET scans, blood tests for tumor markers, and biopsies. I was able to find out more about staging techniques and histological analysis for several tumor types. The major problem in this area is that heterogeneity and genomic instability of tumors makes it often very difficult to prognosticate a patient or to chose the appropriate treatment: Lung cancer patients with similar disease stages can have dramatically different outcomes, and it is still debated which subgroup of breast cancer patients significantly benefits from adjuvant chemotherapy. Furthermore, metastatic breast cancer cells can be dormant for decades, and patients will never have complete certainty whether they are cured or if their disease will recur in the form of brain or bone metastases years later. In addition, some types of cancers are diagnosed very late, because they remain asymptomatic for a long time, such as lung cancer, or they present with very unspecific symptoms, such as colon or pancreatic cancer, and there are often no or insufficient standardized screening tools to detect these types of cancers early.

Long term impact: 
The knowledge I acquired has definitely influenced the way I can interpret findings that I make while working on my own project. But I am also more capable of putting other cancer research projects into context and to better understand the approaches and potential benefits of these projects. But most importantly, I feel that knowing the clinical side of disease research is something that any scientist should possess! I feel more confident when interacting with non-scientists, because most questions that people ask are of a clinical nature. And I have no doubt that this knowledge will have a huge impact on my career in the field of cancer research.

Impact on thesis research: I am currently working on eIF3e’s role in translation using S. pombe (fission yeast) as a model system. One of my goals is to identify specific translational targets that require eIF3e for co-translational quality control during stress conditions. Once these candidate genes are discovered, they will be validated using a mouse model which expresses a mutated form of eIF3e in the mammary alveolar epithelium. This truncated protein leads to the development of persistent hyperplasia and mammary tumorigenesis. My clinical knowledge about breast cancer will help me to interpret the findings we make in this mouse model and evaluate the clinical significance of the results.

Student-specific experiences:
The Med-into-Grad program gave me the opportunity to learn about cancer as a disease in a way that I would never be able to learn from textbooks, lectures, or in the lab. I think this knowledge is extremely important for anyone who does research on any type of disease. Knowing how cancer cells behave in the human body will influence my interpretations of observations I make in the lab, because I automatically put them into context. Furthermore, some of the cases I observed really made me realize how little physicians can do to help certain patients, and this feeling of helplessness reminded me of the importance of my own research, and how crucial it is not to lose focus of our goals. Sometimes a researcher’s main consideration for taking on a project is seems be funding and guaranteed publications, but disease impact is becoming less important.

Advice for new trainees--Autumn preparatory quarter:
The Histology self-study is definitely very useful. Take advantage of the slide set and microscope that is offered. And the “Science-meets-the-medical-patient” class is one of the best classes I ever took! It is very helpful to read the papers that they send out each week before class.

Advice for new trainees—Winter clinical training quarter:
I attended as many tumor boards, lectures, outpatient clinics, and inpatient rounds as I possibly could, because you always learn something new. Many of those start early, so be prepared for that! And definitely ask the attending or fellow questions during rounds or clinics, they are very happy to answer them, but make sure not to interrupt them when they seem very busy – sometimes there are a lot of consults they need to complete. But there’s always a good moment for asking a question, just use common sense. I also found it very useful to make notes, especially during rounds, because you get to follow patients, sometimes over several weeks, and it is easy to forget details when you get to meet 10 to 15 patients a day in rounds and in the clinic.

Take home perspective on Med-into-Grad at UCSD: 
I think Med-into-Grad is an amazing program, I am very grateful that I got the chance to participate, and I highly recommend it to anyone. I ended up learning even more than I imagined I would, and this experience has really had a huge impact on me. And Mark did an amazing job at organizing everything.