February 2012 Spotlight - Catherine Howard
Catherine “Brie” HowardTulane University School of Medicine
Department of Physiology.USA
Current Position: Candidate for MD/PhD Degree, Tulane University Physician Scientist Program, New Orleans, LA
Previous Training: Summer Undergraduate Research Fellow (2003, 2004), University of Texas Southwestern Medical Center, Dallas, TX
When did you become interested in research relating to Hypertension?
Following Hurricane Katrina, I experienced a strong calling to return to my hometown and to help rebuild. Upon enrolling at Tulane University in the Physician Scientist Program and beginning my preclinical mentorships at Tulane Hospital and Internal Medicine Specialists, I became acutely aware of the unholy trinity plaguing a majority of my future patients- obesity, diabetes, and cardiovascular disease. With this knowledge in mind, and a persistent desire to undertake clinically relevant research, I joined the department of physiology for my graduate school studies and became intimately involved in renal physiology and the kidney’s involvement in the development and maintenance of hypertension.
Describe your research interest & the research program that you are in.
Research activities are oriented towards assessment of the pathophysiological mechanisms of hypertension resulting from increased activity of the circulating and intrarenal tissue renin-angiotensin systems (RAS). Emphasis is focused on investigating the unique, blood pressure-independent mechanisms, mediated by activation of intrarenal RAS, involved in the renal functional and morphological derangements that occur during induction of ANG II-dependent malignant hypertension. Current studies will allow determination of the direct effects of selective intrarenal RAS blockade on tubuloglomerular feedback in the absence of reductions in arterial blood pressure or circulating RAS. A variety of in vivo renal clearance procedures and micropuncture techniques are employed to evaluate whole kidney and single nephron hemodynamics and tubular reabsorptive function in anesthetized normotensive and hypertensive rats.
How did you hear about ISH and its activities?
My department chair, Gabby Navar, asked if I would be interested in getting involved in the Trainee Advocacy Committee. It was through the TAC, combined with participation in the High Blood Pressure Research Conferences the past 3 years, that I became familiar with ISH.
What do you consider to be your most substantial scientific contribution so far?
My mentor, Kenneth Mitchell, has access to one of only four breeding colonies of Cyp1a1-Ren2 transgenic rats with inducible expression of the mouse Ren2 renin gene, a model of hypertension that allows clamping of extrarenal levels of renin and ANG II as well as titration of the severity of ANG II-dependent hypertension. Using this model and the direct renin inhibitor, aliskiren, I have succeeded in targeting intrarenal production of ANG II and can show that, independent of changes in blood pressure or circulating levels of ANG II, ANG II produced within the kidney exerts significant increases in sodium and water reabsorption. Furthermore, blockade of intrarenal production of ANG II lowers urinary ANG II excretion, suggesting that urinary ANG II levels reflect intratubular production and/or secretion of ANG II into the tubular lumen. The manuscript outlining these studies has recently been published in the American Journal of Physiology-Renal Physiology. This research has been presented at 2011 Experimental Biology and 2011 High Blood Pressure Research conferences.
Which conference did you first attend & in which one did you first present?
My very first conference attendance was 2001 American Association for Cancer Research in New Orleans, LA, during my junior year of high school. The atmosphere of nearly 13,000 participants was rather overwhelming for me, but my AP Biology teacher, Susan Gingold, knew what she was doing when she brought me. She was planting a seed of curiosity and laying a foundation for a future research career. My first conference presentation was a poster at 2009 High Blood Pressure Research conference in Chicago, IL. That conference was much more specialized with fewer attendees, but the concentration of knowledge and the opportunity for dialogue was unsurpassed.
What upcoming conferences will you be attending and what is the farthest you have traveled for a conference?
I plan to attend 2012 Experimental Biology conference in San Diego. The farthest I have traveled for a conference is Lindau, Germany. I was a delegate from the United States for the 61st Lindau Meeting of Nobel Laureates. Although I did not get to present my original research, I believe this one conference did more to enhance opportunities for national and international collaboration than any other meeting of young researchers I have ever attended.
What is your favorite manuscript from a lab other than your own?
Crowley SD, Gurley SB, Herrera MJ, Ruiz P, Griffiths R, Kumar AP, Kim HS, Smithies O, Le TH, Coffman TM. Angiotensin II causes hypertension and cardiac hypertrophy through its receptors in the kidney. Proc Natl Acad Sci: 103:17985-17990, 2006.
This elegant and inspired study showed conclusively that the receptor-mediated actions of ANG II exclusively at the level of the kidney occupy an essential position in the development of hypertension and its progression to certain associated comorbidities such as left ventricular hypertrophy and cardiac injury.
What entity (ie equipment, patient population) is essential to your research?
As previously mentioned, our lab maintains a breeding colony of transgenic rats that have inducible expression of the mouse Ren2 renin gene (strain name: [TGR(Cyp1a1Ren2)]. This model of ANG II-dependent hypertension allows clamping of extrarenal levels of renin and ANG II as well as titration of the severity of the hypertensive state. Without surgical or pharmacological intervention, we are able to produce a model of slowly-progressive hypertension or a model of malignant hypertension from the same population of rats.
Describe your most memorable (proudest) moment in research so far?
My mentor, Dr. Mitchell, and my chair, Dr. Navar, have been encouraging me to apply for a grant since I first joined the department. During my first year, my excuse for not applying was that I had not identified a dissertation topic and did not know enough about the current environment of hypertension research to adequately generate a specific aims page, much less a whole grant application. During my second year, I was far too busy generating data for my dissertation, writing manuscripts, and applying to conferences to devote 2 months to writing a grant. In the middle of my third year, the papers were done, the rat colony had been depleted, and the only excuse I had left was fear. I was afraid of failure and afraid of what that failure would mean to my future as an independent researcher.
Interestingly, once I understood the source of my reluctance to pursue a predoctoral fellowship, I cultivated a mental attitude to counteract my fear. I began to see completion of the grant application itself as the primary end point rather than reception of the fellowship. Success would come from the knowledge I gained during the application process. During the subsequent 2 months, I learned how to navigate the office of grants and accounting at Tulane, how to express complicated concepts in a succinct and clear way, and how to make every word count on a specific aims page. Most importantly, I learned how to ask an important question, generate a hypothesis based on preliminary data and current understanding, and design experiments to adequately test that hypothesis. My most memorable moment in research is the day I turned in my first completed fellowship application to my grants officer. The day I learned it was to be funded is a close second.
What area of research do you wish you knew more about? Do you have any suggestions for other young scientists?
My family in general has been blessed with good cardiovascular health and longevity. However, we are plagued by autoimmune disease. While hypertension research satisfies my desire to aid in improving the quality of life for my fellow New Orleanians, I have a personal stake in learning how the immune system functions normally and which are the genetic and environmental triggers causing it to run amok and recognize self as foreign.
I have often heard that the most important element of a student’s graduate education is not the dissertation topic, but rather the ability to think critically about that topic. Developing that critical eye comes from reading the current literature, participating in discussions about the cutting edge of one’s field, and offering up one’s own perspective for constructive criticism. My advice to other young scientists would be to find your voice early and to use it often. Just because we are young does not mean our contributions are worth less than those of our forebears. Our minds and ideas are not yet fettered by conventional thinking and traditional understanding, and that is what makes us such valuable resources to our departments and colleagues.