Anatomy and Cell Biology

  • Tootle, Tina

    About: Tina Tootle, PhD

    What is your hometown?

    Waldorf, Maryland, a suburb of Washington D.C.

    When did you join the University of Iowa faculty?

    August 2009.

    How/when did you become interested in science and medicine?

    My interest in science began in high school. I became involved in two science projects.

    • In my first project, I studied temperature regulation of gene expression in bacteria. I had the amazing opportunity to go to the Naval Research Labs where I poured bacteria plates in a hood. Taking an incubator home, I grew bacteria at different temperatures. I discovered that the colonies turned different colors based on temperature, illustrating gene regulation.
    • For my second project, I studied neurotransmitters in rats at the National Institute of Mental Health (NIMH). After injecting drugs into rats, their brains were dissected. I extracted the neurotransmitters from the brains and analyzed them using a mass spectrometer.

    Additionally, I saw human nasal passage neurons growing in culture. Looking through the microscope at these gorgeous cells is what really hooked me.

    What interested you to pursue a career in Biochemistry?

    After high school, I thought I would become a microbiologist for CDC

    As an undergraduate, my first lab experience was studying the effects of transgenic plants on resistance to Colorado potato beetles. Next, I worked 2.5 years in a plant genetics lab researching Arabidopsis plant-pathogen interactions. This is where I learned what it means to do research. I had my own project, presented at lab and joint group meetings, went to a national meeting, and contributed to papers. This experience prepared me for graduate school.

    My interest in medical research was always there and during graduate school, I had the opportunity to pursue medically relevant research. I studied Ras/MAPK signaling and the Retinal Determination pathway using the Drosophila eye as a model system. The Ras/MAPK pathway has key roles in cancer. Retinal determination genes are required for eye development, and mutations in them cause eye diseases.

    Is there a teacher or mentor who helped shape your career?

    I have been truly blessed with great mentors.

    • If it weren’t for my high school teacher, Mr. Brinjak, taking me to NIMH, I do not know how strong my science/research interest would have been
    • Dr Jane Glazebrook, my undergraduate mentor, really treated me like a part of the lab staff and encouraged me to go to graduate school
    • My graduate mentor was Dr. Ilaria Rebay. She taught me an immense amount from presentation skills to project development to scientific writing
    • Dr. Allan Spradling, my postdoctoral mentor, inspired me to think about science at a deeper level, and to always maintain a positive attitude

    How or why did you choose the University of Iowa?

    I had met Dr. Diane Slusarski, Interdisciplinary Graduate Program in Genetics, through a non-science connection. This was my first introduction to the university. Through those same connections, I heard about a faculty position. I applied, was interviewed, and offered the position.

    From my interview, it was clear that the scientific community at Iowa is engaged. They ask good questions. One on one interactions were fabulous, and the chalk talk revealed that I would have good colleagues. Additionally, the open and collaborative nature of the faculty at the university really struck me.

    The University of Iowa’s faculty members are united to provide exceptional patient care while advancing innovations in research and medical education. How does your work help translate new discoveries into patient-centered care and education?

    Non-steroidal anti-inflammatory drugs like aspirin have a variety of effects on the body, from relieving pain to reducing the risk of heart attack, stroke, and some cancers. However, these drugs also have detrimental effects including bleeding disorders and stomach ulcers. To design specific therapies for each action of these drugs, a mechanistic understanding of the events that are inhibited by such drugs is required.

    The focus of my research is to uncover such mechanisms, with the future goal of contributing to the design of therapies to target the newly identified factors.

    What kinds of professional opportunities or advantages does being a faculty member at an academic medical center provide?

    Faculty have the opportunity to interact with both clinicians and researchers, and have access to incredible resources including the tissue repository, the Institute for Clinical and Translation Sciences, and the Holden Comprehensive Cancer Center. Additionally, there are seminars on everything from basic to clinical science, which reflects the wide breadth of expertise at the university.

    Please describe your professional interests.

    While people have been using aspirin (and the plant that produces it) for thousands of years, we know surprisingly very little about how aspirin acts at the cellular levels.

    Aspirin is a non-steroid anti-inflammatory drug (NSAID). These drugs have numerous beneficial effects on the body: they relieve pain and inflammation, reduce the risk of heart attack and stroke at low doses, and reduce the incidence of certain cancers (colon and breast are the best studied). However, these drugs also cause bleeding disorders, stomach ulcers, and at high doses, cardiovascular complications.

    NSAIDs act by inhibiting the cyclooxygenase or COX enzymes. COX enzymes produce the prostaglandin intermediate, PGH2, which is further processed by synthases into active prostaglandins (PGE2, PGF2, PGI2, and PGD2) and thromboxane (TXA2). Prostaglandins are lipid signaling molecules. When one takes an aspirin, one is altering the production of multiple prostaglandins and messing up multiple signaling pathways. Thus, it is not surprising that NSAIDs have so many effects.

    If we want to target a particular action of prostaglandins, for example cancer, then we need to understand the specific prostaglandin signaling pathways involved and their downstream targets. It is these targets that ultimately regulate the biological outcome.

    One target of prostaglandins is the actin cytoskeleton. Actin is the most conserved protein across all animals and is the most abundant protein in the cell. The actin cytoskeleton is dynamically rearranged to mediate cell proliferation, shape, and migration─all of these processes play critical roles in cancer development and subsequent metastasis.

    While prostaglandins are known regulators of the actin cytoskeleton, how they do this remains unknown.

    The main question my lab is working to address is what are the mechanisms by which prostaglandins regulate the actin cytoskeleton.

    The main system we use to address this is fruit fly oogenesis. We use the fly because it is an inexpensive, rapid, simplified genetic model system. Oogenesis or follicle development provides an adult tissue that requires prostaglandin-dependent actin remodeling. By taking advantage of fly genetics we are screening to identify novel downstream targets through which prostaglandins regulate the actin cytoskeleton; importantly the targets we have identified so far are widely implicated in cancer but have not been previously linked to prostaglandins.

    What led to your interest in your focus?

    When I went to the Spradling lab, I knew I was going to use fruit fly oogenesis as my model system. When Dr. Spradling suggested looking into prostaglandin signaling in the fly (which had never been done before), I knew I had found my project. As prostaglandins are known regulators of female reproductive events from cockroaches to humans, it seemed likely that prostaglandins would also regulate fruit fly oogenesis.

    During my postdoc years, I identified the Drosophila COX-like enzyme Pxt and established its roles in regulating follicle development. One of the most striking defects during oogenesis was the failure to undergo a dynamic actin remodeling event that is required for the generation of a viable egg.

    How does working in a collaborative and comprehensive academic medical center benefit your work?

    Everyone is always willing to help, from providing a reagent for a pilot experiment, to teaching you a new technique. This is an invaluable resource. For example, we are currently expanding the lab’s research to include human cancer cell lines and hopefully in the near future, mouse models of cancer. This would not be possible without many collaborative colleagues.

    What are some of your outside interests?

    Photography.

    Do you have an insight or philosophy that guides you in your professional work?

    • Never ignore unexpected results
    • Follow the science wherever it leads you

    If you could change one thing about the world (or the world of medicine/science), what would it be?

    • Having scientific research accessible to the general public, including governmental representatives, and helping them to understand why it is necessary
    • As researchers, we need to be pushed to interact more with the public and make our findings understandable to the average person

    What is the biggest change you’ve experienced in your field since you were a student?

    • The magnitude of the data being generated. Birth of all the -omics.
    • The need to do interdisciplinary and, therefore, collaborative science

    What one piece of advice would you give to today’s students?

    • Learn a variety of approaches both at the bench and in bioinformatics
    • Don’t be afraid to seek outside help to get the advice and guidance you need for you to succeed experimentally
    • And enjoy the journey!

    What do you see as “the future” of medicine/science?

    I hope the future of science is a continuation of both foundational and clinical research. Both types of research are necessary for the advancement of human health, and neither can truly succeed without the other.

    In what ways are you engaged with the greater Iowa public (i.e., population-based research, mentoring high school students, sharing your leadership/expertise with organizations or causes, speaking engagements off campus, etc.)?

    Junior mini-med school: 21 high school students came to visit my lab and learn how we use fruit flies to understand how aspirin works. This resulted in photos and a blurb in the Daily Iowan. http://www.dailyiowan.com/2013/04/18/Metro/32910.html.