Department of Biological Sciences - Lehigh University

Volume 10, 2014 - Biological Sciences Newsletter - Spring 2014

In this edition.....

Please contact us if you would like a PDF of the print version of this newsletter.

Connect with us through our Facebook page

 

 

 

 
Katherine Donigan, Ph.D.

Every year the department of biological sciences sees many prospective students and their families walking the halls, meeting with faculty, and learning about what makes Lehigh University different from other quality research institutions. Thirteen years ago one such student came to campus so she could learn more about our department. This student saw that the research opportunities available for undergraduates in the department are unique and decided to call Lehigh home for the next four years. She would go on to become a Goldwater Scholar (’04), graduate with highest honors with a degree in molecular biology (’05), move on to Yale University to earn her doctoral degree in genetics (’11). She would then become a postdoctoral researcher at the National Institutes of Health.

You would have every reason to ask, just how did

Katherine Donigan

find herself in the halls of the United States Senate working in the office of Senator Elizabeth Warren? Dr. Donigan graciously agreed to answer this, and other questions.

Why did you attend Lehigh University?
I chose to attend Lehigh specifically because of the emphasis that Lehigh places on the undergraduate research experience. When I visited Lehigh in 2001 as a prospective biology major, I was given a tour of the labs at Mountaintop Campus by Dr. Lowe-Krentz and met with several faculty members, all of whom emphasized Lehigh’s commitment to providing undergraduates with the ability to pursue an independent research project with a faculty mentor. After visiting several other top tier research universities, it became clear that the research opportunities available for undergrads at Lehigh were unique and would well-position me to apply to graduate school.

How did being a Goldwater Scholar impact your time at Lehigh?
The Goldwater Scholarship application was one of my first experiences with developing a scientific proposal. I learned a great deal during that process, including how to read and analyze primary literature and how to draft a hypothesis-driven research proposal. These skills were really valuable as I continued my undergraduate research work and drafted my final thesis, and continued be used in graduate school, particularly when I was preparing for my qualifying exams.

How did research play a role in your time at Lehigh?

Katherine Donigan, Ph.D.
Kate Donigan ('05) presenting her research at the
American Society of Andrology meeting

I started working in Dr. Bean’s lab the summer after my freshman year, studying the subcellular localization of a human sperm transmembrane protein, alpha-L-fucosidase. This enzyme is thought to play a role in sperm-egg interactions during fertilization. Using a fluorescently labeled substrate and confocal microscopy, I was able to localize the enzyme to different regions of the cell, and show that the enzyme’s location changed depending on the cell’s physiological state. The dynamic nature of alpha-L-fucosidase suggests that it has a specific function during fertilization.

I worked in Dr. Bean’s lab through graduation, and the summer before graduate school. Being able to work on an independent research project continuously for over two years allowed me to really develop the project and generate meaningful results. With Dr. Bean’s support, I was able to present my work at the annual meeting of the American Society of Andrology, which was a fantastic experience to have as an undergraduate. I was also able to collaborate with Dr. Bean’s graduate student, Jennifer Venditti, and serve as a contributing author on one of her publications.

Describe your research while at Yale University.
I was in the genetics department working for my adviser, Dr. Joann Sweasy. My graduate work focused on base excision repair, one of several DNA repair mechanisms that fix around 10,000 damaged DNA bases in each cell every day. If left unresolved, these damaged bases can lead to DNA mutations, and ultimately, cancer.

I studied DNA polymerase beta, the primary enzyme that puts the correct base back into DNA after the damaged base has been removed. I sequenced POLB, the gene coding for DNA polymerase beta in a large collection of human tumors and identified variants present in tumors but not in normal tissue. I then evaluated the biochemical and cellular properties of these variant enzymes and determined that many of them had altered behavior that led to increased mutations and cellular transformation, two hallmarks of cancer. Cells expressing these variants also showed increased sensitivity to specific chemotherapeutic agents, compared to the wild-type enzyme.

These results suggest that variant forms of DNA polymerase beta may drive cancer progression, and that chemotherapeutic regimens could be optimized based on which variant is expressed in a patient’s tumor. Since the variant enzymes are only expressed in the tumor cells, the drugs would kill tumor cells with less side effects on the normal cells in the patient’s body.

Katherine Donigan, Ph.D.
Katherine Donigan in her lab at Yale University

What kind of research did you do at the National Institutes of Health?
I trained as a postdoctoral fellow for two years with Dr. Roger Woodgate in the Laboratory of Genomic Integrity at the National Institute of Child Health and Human Development (NICHD). The NIH intramural research program is a wonderful place to do a postdoctoral fellowship - it provides top-notch scientific training, opportunities to do a detail in other offices (including policy offices), as well as career counseling, with equal emphasis on academic and non-academic jobs. I was able to engage with my policy interests at NIH by joining a science policy discussion group and writing for the group’s blog (sciencepolicyforall.wordpress.com).

As a postdoc, I was able to build upon my graduate work by studying mechanisms of DNA damage tolerance, specifically the ways that cells can continue to replicate their DNA through damaged regions. I focused on two specialized, error-prone DNA polymerases (iota and eta) that are capable of bypassing damaged DNA. Using biochemical techniques, I evaluated the ability of these polymerases to incorporate ribonucleotides (NTPs) instead of deoxyribonucleotides (dNTPs) during DNA synthesis. I determined that DNA polymerase iota is capable of incorporating NTPs when copying both damaged and undamaged DNA. Incorporation of NTPs in DNA generates strand breaks, which results in genomic instability that may lead to cancer. I further investigated the structural basis for NTP incorporation by selectively mutating specific enzyme residues near the active site and identified the single amino acid that acts as a steric gate to limit NTP incorporation.

How did a scientist end up working on Capitol Hill?
In 2013, I was fortunate to have been selected as the 12th Genetics & Public Policy fellow. This fellowship is co-sponsored by the American Society of Human Genetics (ASHG) and NIH’s National Human Genome Research Institute (NHGRI). The fellowship is designed for early-career genetics professionals who are interested transitioning to a policy career focused on genetics health and research policies at the national level. I spent the first five months of my fellowship working in the policy office at NHGRI, where I drafted policy briefs and attended Congressional hearings on issues related to genetics and genomic medicine. I began the second part of my fellowship in January 2014 as a Congressional health fellow in Senator Elizabeth Warren’s office. As a Congressional fellow, I work with Senator Warren’s health policy team on a wide variety of legislative issues, including healthcare and biomedical research. This fall, I will conclude my fellowship by working at ASHG to gain experience in the area of non-profit science advocacy.

Any interested alumni with advanced degrees in genetics or a related field (which includes genetic counseling or molecular biology) can obtain more information about the Genetics & Public Policy fellow by clicking here. This year’s application is open through April 25, 2014.

How has working on Capitol Hill impacted your life?
The fellowship has provided me with a way to bridge my experience as a bench scientist with my longstanding interest in policy, and my research background has really helped me during my fellowship. Scientists are trained to review and analyze data with a critical eye, skills that are important for working in policy. It’s been exciting to interact with people who share my passion for supporting scientific and biomedical research, and the experience has reinforced my interest in a policy career. After my fellowship concludes this year, I hope to continue my career in science and health policy, either within the federal government or in the non-profit advocacy sector.

Katherine Donigan, Class of 2005
Katherine Donigan, Class of 2005

Can you share the impact undergraduate research had on your education while at Lehigh, and how it prepared you for your time at Yale, and now in your career?
Lehigh’s advanced undergraduate courses and labs in molecular biology, biophysics and biochemistry provided a solid foundation that prepared me very well for my graduate courses. As an undergraduate, I was able to take what I was learning in my coursework and apply it to what I was doing in the lab. My undergraduate research experience helped to solidify my passion for science and gave me the skills and the confidence that helped me succeed in graduate school. Getting early exposure to primary literature, writing research proposals, and presenting data at a national meeting provided ideal preparation for entering graduate school. The analytical skills developed during my scientific training are incredibly useful in my current position when I am analyzing data related to an issue that will provide background and inform policy recommendations.

What advice you can give to today’s generation of Lehigh students?
I would advise students to make sure they are taking full advantage of all the opportunities that Lehigh offers. In addition to conducting independent research and attending a conference, I was able to get introductory teaching experience leading study sessions for organic chemistry. By having diverse experiences, you will learn more about what you like and what you don’t like (which is just as important!)

I would also advise today’s Lehigh students to think about what it is that they like to spend their free time reading and talking about, what really excites them. When considering your future career, try to find a way to merge your academic interests with your personal ones. There are lots of ways to be involved with science outside of the lab, and if the lab is what you love then go for it!

I think the most important piece of advice I could give is to recognize the importance of having a great mentor who provides meaningful support and a balance between guidance and independence.

In the Spring of 2013 we were honored that you attended the department’s undergraduate research symposium and spoke with students about your career path. How did it feel coming back?
Returning to Mountaintop campus was wonderful, and even though it had been 8 years since I graduated, it felt like I’d never left. It was great to see that there are still so many students involved in research, and I was really impressed by the level of work they were doing and by how it was presented. I was happy to discuss the impact that Lehigh had on my graduate and postdoc experiences. I also wanted to let the students know that there are many different career paths available to them, and that the training they were getting in biology at Lehigh would leave them well prepared for whatever path they chose. It was also great to reconnect with many of my former professors, to update them on my current work and to credit my undergraduate experience for launching my career in science.

 
     
   
       

Murray Itzkowitz, Chair | Michael Behe | R. Michael Burger | Lynne Cassimeris | David Cundall
Matthis Falk | Julie Haas | M. Kathryn Iovine | Michael Kuchka | Gregory Lang | Linda Lowe-Krentz | Julie Miwa
John Nyby | Amber Rice | Jeffrey Sands | Jill Schneider | Neal Simon | Robert Skibbens | Jennifer Swann | Vassie Ware