Pharmacy Faculty Excel in research

UNLOCKING THE

BRAIN’S SECRETS

BY GEORGIANN POTTS

photos by Emerald McIntyre

DR. Karen Briski has always had a healthy curiosity about many things. That curiosity has not only led her on a career path to the highest levels of scientific research, but has also made for a rich and interesting life. Early on, Briski wanted to understand the measurable principles that govern the physical world. Later she became very curious about how those principles impacted survival --- specifically how living organisms could overcome internal and external challenges by applying those principles.

EARLY EDUCATION

Briski was born in Phillipsburg, Warren County, New Jersey, and grew up in nearby Oxford. As a young girl she wasn’t sure exactly what specific profession she would adopt, but her love of analysis was certain to influence her ultimate decision. She very much wanted a career that would involve the application of analytical methods. “I cannot remember a time when I did not envision a career that did not involve opportunities to investigate and devise solutions to

problems that impair human and animal health and well-being,” she explains.

With that general goal in mind, Briski earned a Bachelor of Science degree in biology at Albright College in Reading, Pennsylvania. She then earned the Master of Science and Ph.D. from the University of Michigan in Ann Arbor in anatomy. Her doctoral research focused on neuroendocrine regulation of brainpituitary gland communication involved in the control of reproductive hormone secretion. Her early interest in brain

Dr. Karen Briski instructs students in her fast-paced lab in the Bienville building.

function and the impact that various hormones had on it became the catalyst for much of her later research including that in Type-1 diabetes. There is no history of diabetes in her own family that might have turned her toward the study of this disease. Briski nevertheless realized that coping with the reality of Type-1 diabetes created a major threat to the quality of life for countless children and adults. She became determined to conduct research that might help alleviate that debilitation.

In 1999, Dr. Briski and her husband, Dr. Paul W. Sylvester, currently Pfizer Endowed Professor of Pharmacology and Director of Graduate Studies and Research in the ULM College of Pharmacy, accepted faculty positions at ULM. Available resources and facilities were “modest, but sufficient” so they believed that the level of research that they wanted to do would be possible. Since that time, they and a critical mass of dedicated researchers in the Department of Basic Pharmaceutical Sciences have utilized various means

“I CANNOT REMEMBER A TIME WHEN I DID NOT ENVISION A CAREER THAT DID NOT INVOLVE OPPORTUNITIES TO INVESTIGATE AND DEVISE SOLUTIONS TO PROBLEMS THAT IMPAIR HUMAN AND ANIMAL HEALTH AND WELL-BEING.”

– DR. KAREN BRISKI

to establish an impressive state-0fthe-art instrumentation infrastructure that supports individual and collaborative research initiatives.

Briski was appointed Director of Research and Graduate Studies in the College of Pharmacy in 2000 and over the next several years worked diligently to educate a variety of audiences --- including investigators at other Louisiana universities --- as to the research expertise and capabilities of the ULM faculty. This led to ULM’s College of Pharmacy being included in several inter-institutional consortia. Her advocacy was invaluable to growing awareness of the College of Pharmacy.

In 2005, Briski was named Head of the Department of Basic Pharmaceutical Sciences for ULM’s College of Pharmacy. This additional responsibility meant that she now divides her time in three areas: administration, teaching, and research. Both her teaching and research activities have helped her to be a better administrator. Her administrative responsibilities are not carried out “in

a bubble” in the office. Instead, her decisions relating to her department reflect her ongoing real-time experiences in the classroom and the laboratory.

TEACHER/RESEARCHER

Briski loves to teach, and is by all accounts an excellent teacher. Among Briski’s favorite teaching responsibilities is lecturing to incoming, first-year professional pharmacy students in Pathophysiology-I, a course offered each fall. Her lectures cover two areas including how the body maintains a balance of important macro- and micronutrients that support cell function, and nervous system structure and function (Briski’s specialty). “I am one of the ‘front-line’ instructors,” she says. “One of our primary responsibilities is to outfit professional pharmacy students with the necessary knowledge for a successful career in pharmacy while instilling in them the importance of research.”

of a strong, collegial relationship with their peers as they work in teams. This enables them not only to learn a wide set of complex skills, but to do so through a process that takes much less time than if they were working as an isolated individual. Through this process of helping each other, her students realize that when one individual succeeds, the entire group succeeds. “My students are the lynchpins of my laboratory operations,” she says. “I gladly observe daily many instances of my people selflessly assisting each other in their work.”

STUDENT SUCCESS

Simply stated, Briski sees every research project as a vital teaching vehicle. Her students benefit from this attitude in ways that continue to pay dividends as they pursue their careers.

One of the most important measures of a professor’s success is the success of his students in the careers that follow their formal education. Briski’s former graduate students can now be found working in a variety of prestigious universities including John Hopkins University, Washington University in St. Louis, the University of Connecticut, the University of Maryland, the University of Illinois – Urbana Champaign, and the University of Michigan. These former students are conducting important research in their own right, and are publishing in peer-reviewed journals. They are in large measure a part of ULM’s and Briski’s legacy.

For Briski, the lines between teaching and research are blurred. She sees time in the laboratory as quality teaching time as well as research time both for herself and for her students. Briski has her graduate students perform all aspects of the actual research work so that she can teach them relevant laboratory skills and techniques that will serve them well when they graduate and are working in laboratories as part of their careers. By doing this, her students acquire an aptitude for developing exciting and creative hypotheses based upon the current knowledge in the field. “They become both practiced in analyzing and interpreting experimental outcomes and also skilled in communicating their results in both written and spoken form” she explains. “We establish a feasible working premise, identify the tool set that will be needed to test that hypothesis, ensure that appropriate equipment is available to carry out the proposed work, and then evaluate outcomes within the context of current knowledge.”

“FOR SOMEONE COMING FROM THE EASTERN PART OF THE WORLD, DR. BRISKI AND ULM WERE MY EYES TO LOOK AT THE WESTERN VALUES OF EQUALITY, UNITY, AND TEAMWORK. THESE VALUES --- PLUS THE HIGH QUALITY EDUCATION I RECEIVED FROM THE LECTURE ROOM AND LABORATORY --- HAVE HELPED ME TO CONTINUE MY ACADEMIC JOURNEY AFTER THE PH.D.”

— DR. BAHER IBRAHIM

Dr. Pratistha Tamrakar, a 2015 ULM graduate with a Ph.D. in Pharmaceutics and Drug Design, credits Briski with much of her own success. Briski was her major advisor, and was instrumental in guiding Tamrakar through the rigorous doctoral program of study. “She was the best mentor I could ask for, always supportive and always ready to help me with my project,” Tamrakar remembers. “Working under her supervision has made me a detail-oriented and motivated scientist --- both of which I think are the most essential qualities that made it possible for me to earn my Ph.D.”

The atmosphere in Briski’s laboratory is one that fosters both positive communication and mentoring among the students and with their professor. Teambuilding is, according to Briski, “indispensable” for a productive research program. She provides opportunities for her students to observe the benefits

Other former students are just as complimentary. Dr. Baher Ibrahim, 2014 Ph.D. graduate from ULM, joined Briski’s lab after earning the Bachelor’s in pharmacy and Master’s in pharmacognosy from Mansoura

Dr. Karen Briski examines her student’s images of micro-dissected tissue samples which were captured by the Zeiss PALM MicroBeam laser.

University in Egypt. Ibrahim credits Briski for his success. “Dr. Briski’s excellent mentoring skills, continuous guidance, strong support, and full trust in my capabilities were the main reasons for my success,” he explains. “For someone coming from the eastern part of the world, Dr. Briski and ULM were my eyes to look at the western values of equality, unity, and teamwork. These values --- plus the high quality education I received from the lecture room and laboratory --- have helped me to continue my academic journey after the Ph.D.”

Ph.D. journey. Under her supervision, I was able to publish four articles as a first author, and two more as second author. Even though I am thousands of miles away from her, I am still practicing what I have learned from her in both my teaching and personal life.”

ULM is across many research areas,” Sutherlin concludes. “ULM is increasingly shaping its international brand.”

DIABETES RESEARCH FUNDING

Briski’s research proposals have been noticed throughout her career. The latest grant is the sixth that Briski has received from the NIH. In addition, she has received funding from the National Science Foundation, the American Diabetes Foundation, two from the Juvenile Diabetes Foundation, and the Children’s Brain Tumor Foundation. At the moment she is working concurrently on two NIH grants --- one awarded in 2015 and the newest one in 2016.

Clearly Briski’s influence is farreaching and lifelong. Dr. Prem Shrestha, a 2016 Ph.D. graduate from ULM, says simply that completion of his doctoral degree would not have been possible without Briski’s support and guidance. “I will forever be thankful to her,” Shrestha says of Briski. “She was --- and remains --- my best role model for a scientist, mentor, and teacher. Her enthusiasm and love for teaching is contagious.”

Dr. Fahaad Alenzi, a 2016 Ph.D. graduate, has taken the education he earned at ULM and is currently working as an assistant professor at the College of Medicine at the University of Hail, Kingdom of Saudi Arabia. He, too, credits Briski with making the difference in his achieving his academic goals. “Working with Dr. Briski has not only improved my research skills, but has also improved my understanding of thinking like a scientist,” Dr. Alenzi says. “Her way of motivating, encouraging, and supporting was the main helper to me to fulfill my

Dr. John Sutherlin, Executive Director of the Louisiana Research Corporation and Associate Professor of Political Science at ULM, says that Briski “. . . represents the best of ULM”. He points out that Briski, together with many other ULM researchers, have “raised the bar for others” including himself. “Dr. Briski has shown ULM what is possible. She and others continue to showcase how special

Briski’s first diabetes research was funded by the NIH and the American Diabetes Association. Her project was to investigate how the brain uses signals on glucose (a simple sugar in the blood that provides energy) deficiency to inhibit reproductive function. This study of the interaction between the brain’s perception of a low blood sugar rate and that perception’s impact on reproduction led to subsequent awards

from the Juvenile Diabetes Association.

BRAIN/INSULIN INTERACTIONThese funds allowed Briski and other researchers to study more closely the mechanisms underlying the gender differences in brain responses to blood sugar levels. They noted that the brain became desensitized to repeated insulin-induced hypoglycemia (low

sugar elevation or hunger efficiently. Because the brain uses a significant amount of energy available to the body, when that energy is not readily available there is a significant risk of energy. Nerve cells require a constant supply of energy in order to function properly in all areas, but especially so in neurotransmission or communication. When energy is not adequate, the electrolyte balance across

brain desensitization and the possibility that estrogen might help with blood sugar storage and release led Briski to apply for her most recent NIH grant. In that grant, Briski proposed a series of experiments to learn how estrogen may influence both the size and mass of glycogen reserves in the brain and regulate the release of glucose during low blood sugar episodes in each gender. Briski and her team seek to characterize the mechanisms at the molecular level by which estrogen regulates glycogen metabolism. “Such knowledge will pave the way for development of appropriate therapeutic strategies to boost glycogen protective capabilities to defend the brain against hypoglycemic injury,” she explains.

Briski’s program over the next five years will test her theory that estrogen can be a protector of these neurons as it enhances fuel reserves in the brain. “We wish to leverage insight on how estrogen regulates glycogen to develop a means to manipulate the energy ‘pool’ to offset decreased low blood sugar levels that occur during hypoglycemia,” she says.

Research requires more than a brilliant mind and funding, however. Equally critical is having the right equipment necessary to conduct that research. Because competition for research funding is fierce, it is important that any project proposed for consideration of funding be novel enough to stand out among other applicants, and must have the very best instrumentation available so that the highly technical, very sophisticated analyses can be carried out.

CUTTING-EDGE EQUIPMENT

Dr. Karen Briski proudly sits beside ULM’s Zeiss PALM MicroBeam laser. This cutting-edge microdissection instrument is vital for Briski’s research and securing grants.

blood sugar levels). The importance of this finding was that many Type-1 diabetics have to take daily injections of insulin to control their blood sugar levels, and these repeated doses --- critical for survival --- over the long term were in fact impacting the brain.

Type-1 diabetics experience countless episodes of low blood sugar throughout their lifetimes. These episodes create an unavoidable complication as the patients and their physicians attempt to manage them through insulin. Over time, the brain “desensitizes” and becomes less able to recognize these episodes. As a result, the brain no longer triggers blood

the brain’s plasma membrane cannot be maintained. One result of this is that neurons in specific regions of the brain are likely to die and create lesions.

IS ESTROGEN THE KEY?

Briski had previously studied the role of glucocorticoid hormones (those that control metabolism of carbohydrates and fats) by gender. As a result of this research, she became convinced by the data that estrogen has the ability to enhance both the synthesis and storage of glycogen (the form glucose takes when it is stored in the body for later use).

Seeing the connection between

Two instruments that are vital to Briski’s NIH grant are the Zeiss Laser Catapult Microdissection instrument and the confocal microscope that are in her laboratory. The laser beam of the microdissection instrument allows individual nerve cells from brain tissue to be removed and studied after their neurotransmitter identity has been determined. The confocal microscope is necessary for the best “look” at fluorochrome-labeled molecules (molecules literally stained for ease of tracking) that are used to identify specific proteins or to verify the destination of drug molecules. “These two instruments were provided as part

of my startup package when I became department head,” she says. “Those allowed me to propose creative ‘outof-the-ordinary’ experiments with the high likelihood of addressing lingering unanswered questions in my field. I believe this was viewed very positively by the reviewer of my proposal.”

Briski’s proposal received a very high score when it was reviewed by NIH. To put this in perspective, her proposal was assigned a percentile rank of 3 and an impact score of 20. According to the NIH, the percentile rank is “. . . calculated by ordering the impact score of a particular application against the impact scores of all applications reviewed in the current and the two previous review rounds. An application that was ranked in the 5th percentile is considered more meritorious than 95 % of the applications reviewed.” (See “Paylines, Percentiles, and Success Rates” posted by Dr. Sally Rockey, former Deputy Director for Extramural Research at NIH, in “Rock Talk” February 15, 2011). In other words, Briski’s grant proposal ranked higher than 97% of the competing applications. As a result of this high score, the award was funded for the full amount requested instead of having a reduction in funds for administrative costs. This is highly unusual, and speaks to both the novelty of Briski’s hypothesis and the quality of her research plan.

“DR. FEYNMAN DEVOTED CONSIDERABLE TIME AND EFFORT TO RESOLVE THIS DESPITE SUFFERING FROM A TERMINAL ILLNESS. I WOULD ASK HIM HOW HE GOT TO THE ANSWER THAT HAD ELUDED EVERYONE ELSE.”

When she was asked recently whom she would select if she could speak with any research scientist, living or dead, and what would she want to talk about, her response was perfectly in keeping with her love of analytics. She would like to speak with the late Dr. Richard Feynman, the brilliant theoretical physicist who, among many accomplishments throughout a stellar career as a teacher and researcher, discovered the role that the O-rings played in the space shuttle Challenger disaster. “Dr. Feynman devoted considerable time and effort to resolve this despite suffering from a terminal illness,” she explains. “I would ask him how he got to the answer that had eluded everyone else.”

Surprising, perhaps, is her answer when asked which research scientist, living or dead, would she most like to work along side and what would she want to research. Her answer does not look to the future, but rather turns back time. “I would love to observe the very first health practitioners in humankind, as they had none of the sophisticated technologies and means of communication at their disposal,” she explains, “but relied exclusively on the art and science of observation, deductive analysis, and intuition to build a foundation for the practice of human medicine.”

FUTURE PLANS

For now, Briski is focusing on her diabetes research with the hope that from it will come therapies that will contribute to the management of the disease. Her own laboratory will be expanded, but she sees this going forward smoothly.

There is no doubt that she will continue to generate ideas for projects that she intends to translate into future grant proposals. She has over 100 peerreviewed publications as well as many presentations in regional, national, and international meetings. Dean Blaylock observes, “This type of exposure is a major plus for the institution in terms of recognition of the fundamental research efforts by both her, her graduate students, and her colleagues.”

There is also no doubt that the ULM doctoral graduate students who come under her mentorship and influence will one day become alumni in whom we may all be proud.

In February 2016, the Carnegie Classification of Institutions of Higher Education classified ULM as an “R3” doctoral university for the first time. That classification placed ULM among 109 other universities in the United States holding the ‘Doctoral University’ designation. Previously, ULM had been classified as ‘Master’s College and University – Larger Programs. “ULM’s ‘Doctoral University’ classification reflects the efforts made by many individuals over many years,” ULM President Nick Bruno pointed out. “The administration and faculty worked together to create a strategic plan that would allow us to reach this goal. No less important was the commitment of our outstanding graduate students. Dr. Briski’s work both in the classroom and in the laboratory have played a significant role in ULM’s attaining this designation.”

WHAT IF? Briski is indeed filled with curiosity.

– DR. KAREN BRISKI