Explorer - Winter 2020

Explorer WINTER 2020 . VOLUME 6

PENN DENTAL MEDICINE VERNON BRIGHTMAN RESEARCH SOCIETY NEWSLETTER

EXECUTIVE BOARD

CONTENTS 2

Dr. Esra Sahingur Q&A

3

Student Researchers

4

Dr. Elliot Hersh Q&A

6 Research Day 2020,

Summer Research Panel

7 8

Student Research Programs Dr. Dana Graves Q&A

9 Dr. Kathleen BoeszeBattaglia Q&A

10 Dr. Richard Doty Q&A

Vernon Brightman Research Society Executive Board The Vernon Brightman Research Society (VBRS) Executive Board members for the current academic year include the following individuals. They invite students with an interest in research to join VBRS. PRESIDENT: Ryan Cho, D’21 VICE PRESIDENT: Kailin Baechle, D’22 TREASURER: Noor Rehman, D’22 SECRETARY: Spencer Tazumi, D’21 OUTREACH COORDINATOR: Dane Kim, D’22 EVENTS DIRECTOR: Vu Tran, D’22 D1 REPRESENTATIVE & NEWSLETTER EDITORS:

Julia Jeong, D’23; Rachel Kogan, D’23; and Yilan Miao, D’23

Named in honor of Dr. Vernon J. Brightman, a former Penn Dental Medicine faculty member and strong supporter of student research, the VBRS is the primary student research organization at Penn Dental Medicine. Since its inception, VBRS has helped numerous students find their niche in research at the School. It aims to promote interest, participation, and appreciation of the basic and clinical oral health research that keep dentistry a science and research-based profession.

The VBRS is Penn Dental Medicine’s chapter of the American Association for Dental Research AADR National Student Research Group (NSRG). Dr. Francis Mante, Associate Professor, Division of Restorative Dentistry, is the VBRS Faculty Advisor; reach out to him at mantefk@upenn.edu.

FACULTY Q&A DR. ESRA SAHINGUR Associate Dean of Graduate Studies & Student Research Associate Professor, Dept. of Periodontics Dr. Sahingur joined Penn Dental Medicine in September 2019 as Associate Dean of Graduate Studies and Student Research, providing leadership, strategic vision, and oversight to support and expand the graduate studies and student research endeavors at the School. She will be overseeing the Summer Student Research Program for the summer of 2020. Originally from Istanbul, Turkey, she received her DDS from Istanbul University, Turkey, in 1994 and then moved to the U.S. for her postgraduate education. She completed all of her postgraduate training at State University of New York at Buffalo, receiving a Master of Science degree in Oral Sciences in 1999 and then a PhD in Oral Biology with a clinical certificate in Periodontics in 2004.

How did you get involved in your current research?

I have always been interested in academia since I was a little kid. My parents were my inspiration. After graduating dental school, I got accepted to combined periodontology residency and PhD programs in Istanbul University. After one year in this program, I moved to the U.S. and continued my postgraduate education in SUNY Buffalo.

I got to work with some of the best and brightest minds in our field who inspired me even more to be a clinician and researcher. I obtained a MS degree with a concentration in microbiology and PhD with a concentration in immunology. I also completed a clinical certificate program in periodontology. The advanced training I received both in clinical and basic sciences was instrumental for my current research.

What areas do you perform research in?

We are interested in understanding the role of immune and inflammatory pathways in periodontal disease pathogenesis, genetic and epigenetic susceptibility to periodontitis, and the link between oral and systemic diseases.

What are the main goals of your research?

The ultimate goal of my research is to improve clinical outcomes and patient management. As a clinician, I get to experience the effect of research on daily operations first-hand. I would like for my 2 EXPLORER . WINTER 2020

work to have an impact not only on my patients in the clinic, but also with the wider world. I would like to find something crucial through my research that will help the population and inspire the next generation of scientists and clinicians.

What are some projects that you are currently working on?

We are currently working on defining the biological pathways and key regulatory molecules in the initiation and resolution of periodontal inflammation. We are also studying the effect of natural compounds on these key biological pathways and their utilization in the clinics to improve patient management.

What are the findings or results of your studies?

Our team initiated the studies that revealed the involvement of nucleic acid sensing and ubiquitination in periodontal disease pathogenesis, and more recently, the link between oral cavity, gut, and liver axis.

How will the results of your research be applied?

As a clinician scientist, I am able to focus my research toward projects that will translate to improved clinical care. We always test and validate our results using clinical and preclinical studies. As we enter the new era of precision dentistry, it will be crucial to understand the states of health

and disease in the oral cavity at the cellular and molecular level to develop personalized preventive and treatment options. Our studies focus on addressing all these areas.

What do you enjoy most about doing research?

I think research is like a treasure hunt where you follow the clues to get the big prize. In the case of research, the prize is improving the health of your patients and the clues come from clinical observations and previously published data. I always enjoyed playing treasure hunt and solving puzzles when I was a kid and now I get to do it through research at a very high level and for a much bigger cause. In addition, I enjoy interacting with students and watching them develop critical thinking skills to solve problems through their involvement in research.

Do you have any advice for students who are interested in pursuing research?

Academia is very rewarding. You help your patients in the clinics, educate and inspire the next generation of clinicians and scientists, and get to be directly involved in shaping the future of our profession through cutting-edge research, innovations, and health-care policies. Research encompasses many fields and I would encourage all students to get involved in something they are interested in, and who knows, the prize at the end may be life-changing.

STUDENT RESEARCHERS

Alisa Lee (D’21)

Medical Research Scholars Program, NIH What’s your current research project?

I’m in the Medical Research Scholars Program (MRSP) at NIH. MRSP is a comprehensive, year-long research enrichment program designed for medical, dental, and veterinary students. There are numerous labs in the National Institute of Dental and Craniofacial Research (NIDCR) studying a wide variety of subjects such as bone biology and mineral metabolism, salivary gland function, and immunology. I’m doing research at the NIDCR, focusing on a rare bone disorder called Hyperphosphatemic Familial Tumoral Calcinosis. MRSP will give me the opportunity to dig deep into a research project and learn how to scientifically evaluate past, present, and future oral health care practices to improve patient care.

What qualities do you admire or think are important in researchers?

In research, not every experiment that you do is going to work perfectly. In fact, most experiments will probably result in unexpected or inconclusive data. This is where perseverance and critical thinking come in play. Often you need to adjust experimental conditions to get clear answers to your questions. I admire researchers who do not give up when faced with an obstacle. Remember that the beauty of research is that you get to explore the unknown, solve puzzles, and discover new worlds. Unexpected results might reveal something no one has come across yet. So do not be afraid to fail multiple times! If you run into a problem, take a step back and critically think about what can be changed. Take your passion and push further.

What was the most difficult time in your research?

How did you get over it?

Balancing time can be challenging in research. There are so many questions out there that need to be investigated, but we can only devote so much time to finding the answers. Especially as a student, I had to balance school, work, and research among other day-to-day tasks. Research definitely takes time to learn and it can be daunting at first. However, it’s important to not feel rushed when doing experiments, because rushing often leads to mistakes. For me, I write down everything that I need to do for each day so that I won’t forget. Having an organized schedule allows me to make the most out of my day. I’m still working on balancing my schedule with experiments and meetings, but it gets easier over time.

Any advice for students who are interested in research?

There are plenty of research opportunities at the school and outside school! If you are just getting started, I would recommend that you look at the Penn Dental Medicine research website and see the list of topics that current faculty members study. When you find a few labs that might interest you, email the professor, express your interest, and ask if there are any open positions. Try to find a mentor who is willing to spend the time and provide you with one-on-one guidance, as this can have a positive effect on your overall research experience. The summer research program at Penn Dental Medicine is a good choice if you want to get an idea of what research is like.

Jinnu Kim (D’23) “Student dental research is extremely important, as it opens new doors for clinical practice as well as improves upon current practices we have right now. There are many debilitating dental diseases that may give rise to even more harmful systemic diseases, and with research, we can aim to treat and even prevent these from occurring. Dental research, from the basic sciences to the directly applicable clinical research, is important to helping patients & the general population stay healthy.”

Andrew Casey (D’23) “I think dental research is extremely important as it drives the field forward, and directly impacts what we learn during our classes. It is nice to know Penn has so many opportunities for students to get involved in dental research.”

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FACULTY Q&A DR. ELLIOT HERSH Professor, Dept. of Oral & Maxillofacial Surgery/Pharmacology

How did you get involved in research?

What got you interested in it?

Actually, when I was a dental student, research wasn’t even a twinkle in my eye. During my junior year, a new faculty member came in at Rutgers University. His name was Stephen Cooper and he had gotten his dental degree from University of Pennsylvania and his PhD degree from Georgetown University Medical School. He taught a course in the beginning of my senior year, called “Clinical Therapeutics,” which put a clinical flavor on the basic pharmacology course that we had. After that I was hooked. He was by far the best teacher I had in all of my dental school training.

That January, two postdoctoral fellowships became available for graduating dental students; one was in Immunology with a different faculty member and one was in pharmacology to spend the year working with him. So, I applied, and the rest is history.

Within the first 3-4 months of that one-year experience, another faculty member D.M.D. PhD came on named Paul Desjardins, who is a respected dentist/pharmacologist. They decided they wanted to send someone over to the medical school to get a master’s degree.

They’ve never done that before.

I decided that in order to really get a better understanding of science, ask hypothesis driven questions, be able to write up scientific data, and get things published in journals, this training would be great; and that led to a master’s degree. It also led to the first paper I ever published in “Anesthesia Progress” called “The Effect of Intravenous Meperidine on Various Reparatory Parameters in Normal Volunteers.” Meperidine is a very old opioid. It was a main stay of sedation regimens. We wanted to look if we could pick up some of the pre-morbid signs of respiratory depression at therapeutic dosages, and that was my first bonified research project.

Toward the end of that master’s degree, I realized that if I wanted to learn science to a greater degree, I would need to get a PhD. So I ended up flipping over to the medical school at Rutgers, and they took me, they never had a dentist before. I ended up doing my PhD work with a professor, George Condouris. He was one of the first people to describe that local anesthetic action is due to a blockade sodium influx, so this was a perfect match.

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Both my MS and PhD thesis advisors allowed me to practice dentistry part time so that my wife and I didn’t starve to death. At the time, I applied for an NIH postdoctoral fellowship and it took me two shots to get it, as it usually does. The second time around I was funded and that suddenly put me at a salary level almost equivalent to an assistant professor. So I think having that funding played a role in me being appointed to an assistant professor here. It was a great learning experience as far as getting your writing critiqued, not taking things personally, and getting your research off the ground.

What were some of your previous research projects?

My biggest claim to fame was this study at Penn with 210 subjects in 11.5 months-all wisdom teeth extractions. I did the study that supports the marketing claims that: “for tough pain nothing works better than Advil liquid gels, not even extra strength Tylenol.” It wasn’t even my conclusion at the end of the paper, that wasn’t the main focus of the study.

But, it was clear that this rapid release formulation of solubilized potassium ibuprofen had much greater peak affects even at 200 mg, and much more staying power than maximum doses of acetaminophen (1000 mg).

We did another pivotal study here at Penn that helped get a rapid release formulation of diclofenac FDA approved. Post-surgical dental pain is driven by inflammation and these NSAIDs work as well if not better than addictive opioids. I have been studying non-addictive pain relievers for the greater part of 30 years. The neat thing that we’ve been doing now is trying to predict who the best responders to non-addicting NSAIDs will be prior to surgery, because the time-action curves that I put in papers and give in class are averages. And even in cases with a super-duper pain reliever that works great on average, 15-20% of individuals said it was ok but they needed something more, and 5% said it didn’t work at all.

My other field of research is on local anesthesia. We have done pivotal studies here with injectable and topical anesthetics that put a lot of drugs on the market.

We had a large study involving topical benzocaine, an over-thecounter gel. The FDA challenged us to see if it works on toothache pain. We found that the maximum strength lasted about 20 minutes

longer than the normal strength. I have to give a lot of credit to my research coordinator, Stacey Secreto. I may be a lot of the brains behind the operation, but she’s the one that gets all the data. That was a study that really needed a lot of good timing. We noticed that most of our patients came in on Mondays and Fridays. They were triaged in the oral medicine emergency clinic and were sent to the oral surgery or endodontics clinic for definitive treatment in the following hours. So, we had roughly a 2-3 hour window to approach them and suggest this study.

We didn’t advertise that there was $50 compensation because then everyone would claim to have toothache pain. You always should give people compensation for their time, but you can’t coerce them. Another part of this study was analyzing how well people self-administered the correct dosage of the medication.

We found out that about 80-85% of them actually followed the label and applied the recommended dose. Only 15-20% were using it in excess. The problem with excess benzocaine administration is methemoglobinemia. There was no evidence of it here.

What is some of the research that you are currently working on?

The most exciting stuff that I am doing right now is a collaborative project between myself, my research coordinator, some of the oral surgery faculty, and individuals from the Institute of Translational Medicine and Therapeutics. I became involved with this group simply by going to their meetings. They have a specialized group that focuses on NSAIDs called Personalized NSAID Therapeutics Consortium (PENTAGON).

An MD/ PhD Neurologist, John Farrar, and I presented to this group what we planned on doing. We received funds from Pfizer to do our second functional brain imaging study, to determine what pathways of the brain light up when patients have post-surgical dental pain and what changes when they go from pain, to pain relief.

We wanted to go to fMRI instead of SPECT so we could put people in the scanner and continuously monitor cerebral blood flow as the pain ramped up or down. We would actually wheel them from the oral surgery clinic at Perelman to the basement of HUP to the fMRI. We performed a double blind study, giving them either rapid release ibuprofen, in this case the sodium film tab preparation of Advil, or placebo.

But right before we started we presented at the PENTAGON group, and Katherine Theken PharmD, PhD and Tilo Grosser, an MD cardiologist, asked if we could add some blood and urine samples to the data. So we put that amendment in. It turned out that while the brain imaging data was really interesting and the classic pain areas lit up with orange and red areas in the thalamus and anterior cingulate gyrus, once participants received the medication all of these areas turned blue and returned to normal; with the placebo group, the areas stayed red. That was pretty neat, but even neater was the precious blood samples and urine that we collected.

With this type of research, you can’t be an expert on everything. You need to work with others who have different areas of expertise to get any sort of funding and answer hypothesis-driven questions.

Through these samples, we were able to identify two phenotypes of ibuprofen responders. On average, ibuprofen overpowered the placebo with statistical significance. But if you look individually at patients, there were 10 patients with an average pain score of 7 out of 10, and when dosed with rapid release ibuprofen, at 4 hours

post-dosing they didn’t need anything else. The other group of nine needed another pain reliever between 90 minutes and 3.25 hours.

Everyone in the placebo group needed something in 1.25 hours. We also found that those who were the full responders made the most prostaglandins after surgery. So with partial responders, yes they have pain, but they may have some other mediators that are also driving their pain.

Now we’re doing a bigger study with 80 people. We’re looking at oral microbiome, pro-inflammatory cytokines, sex differences, and genomics. We received a grant from the Center of Precision Medicine to see if there is a way to personalize analgesic therapy.

What are some of the most difficult parts of research and what keeps you going?

Some of the most frustrating parts of research is slow enrollment.

We’re dealing with human research subjects and a lot of personalities with co-investigators. You have to accept that people have different personalities and different mindsets.

Collaborating with others from different schools here at Penn is absolutely fantastic. I have learned so much about brain scans. I don’t have to be an expert on it. It was very frustrating at first, because all of us at Penn put our armor on. But you have to have the guts to ask “wait, I don’t understand, what does this mean? What does noncoding RNA do?”

What keeps me in the game? There are three reasons: 1) I can translate my research into the classroom. I have been very passionate about the addicting effects of opioids ever since 1990, way prior to the zenith of the crisis. 2) The ability to publish things for clinicians about opioid alternatives is gratifying and I think it’s reducing opioid prescriptions. This pain genomic stuff is really slick stuff and even though I’m an old dog, I like to learn new tricks.

3) From a teaching end, I enjoy being around students. The most important thing I do is translating my research to DMD students, residents, and people in private practice.

Do you have any advice to students who are interested in going into research after dental school?

The DMD degree gives students a lot of opportunities. The first project that I think you should choose when approaching a mentor is something that you have a reasonable chance of publishing. One of the issues with some of my studies is that they’re long term and performed while you’re in class. I do have students sometimes, but it is a major commitment.

You need a mentor who enjoys working with students. Dental school is not easy. I remember my plate was pretty full back then and I don’t know if I could have handled going into someone’s lab in addition to everything else.

Do some work on your own — don’t be afraid to ask questions. Ask your mentor some questions if you don’t understand things well after reading the papers. Schedule your time well when you’re going to be in the lab, when you’re going to be studying, and when you’re going to be having some enjoyment. Having no fun can sometimes lead to becoming a miserable person. That’s my major advice. Be prepared for experiments not working out. That’s why they call it research.

Be prepared for research to occasionally not go in the way that you thought it would go.

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2020

SUMMER RESEARCH PANEL

THURSDAY, MAY 14, 2020 Penn Dental Medicine will hold Research Day 2020 on May 14. Research Day is an annual event that brings faculty and students together to share their research activities with one another and spotlight the depth of the School’s research enterprise at Penn Dental Medicine.

The day includes a program of presentations by faculty and invited speakers, along with poster presentations, representing DMD-student and faculty, and junior investigator research.

All Research Honors students and participants in the Student Summer Research program present posters.

In addition, student and junior investigator research will be recognized with the selection of the 2020 AADR Travel Grants. The AADR Travel Grant program was launched by Penn Dental Medicine in 2014 to build opportunities to advance ongoing research and leadership among students and junior researchers; recipients will attend and present their work at the 2021 AADR/CADR Annual Meeting to be held in Boston, MA, March 17-20, 2021.

The Vernon Brightman Research Society supports Research Day, helping with poster session set up and break down and other roles as needed. It is a great day to learn about all the exciting research projects ongoing with students and faculty throughout the School.

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The Vernon Brightman Research Society held a Q&A panel with students representing a variety of research opportunities available to students at Penn Dental Medicine. Panelists provided information about the programs they were involved in, respective programs’ application processes, and anecdotes from their experiences. First-year students were encouraged to ask questions about each program while enjoying lunch.

The panelists included: KAILIN BAECHLE, D’22 Research Honors | kbaechle@dental.upenn.edu YILAN MIAO, D’23 Research Honors | yilan@dental.upenn.edu SYLVIA SAWIRES, D’22 Invisalign Summer | ssawires@upenn.edu TIM WANG, D’21 Leonard Davis Institute Summer Research Program | timwang@upenn.edu MADISON RICHARDS, D’22 VA Implant Study | madir@upenn.edu BRENNA HARRINGTON, D’22 Summer Research Program | bkh1@upenn.edu

STUDENT RESEARCH PROGRAMS RESEARCH HONORS PROGRAM

SUMMER RESEARCH PROGRAM

The Honors in Research Program is open to talented students in their first or second year at Penn Dental Medicine who will plan, implement, and execute a hypothesis-driven research project over a one to two year period. Students will present their findings at Research Day and complete an Honors Thesis at the end of their fourth year.

Within the Summer Research Program, students work full-time in July and August with a faculty preceptor on a mutually agreed upon research project in basic laboratory or clinical sciences. A stipend of $1,000/month is provided to those applicants accepted into the program after review by the Research Committee. The purpose of this program is to provide dental students a chance to experience a “handson perspective,” especially for those interested in pursuing research-oriented careers in the oral health field, thereby promoting dentistry as an academic and research-based medical science. Students will present their findings at Research Day and complete a summary report at the end of August.

REQUIREMENTS TO APPLY: • C omplete the application • 1 st or 2nd year at Penn Dental Medicine • U ndergraduate science GPA of 3.5 • M inimum 3.25 GPA each semester of Dental School • L etter of recommendation from past or current research supervisor • T wo-page research proposal • P roposed timeline for completion of the project APPLICATION DUE DATE: May 15, 2020

REQUIREMENTS TO APPLY: • C omplete the application • G ood academic standing • A vailability to conduct research full time and attend weekly research meetings • R esearch proposal

FOR MORE INFORMATION: www.dental.upenn.edu/researchhonors

APPLICATION DUE DATE: March 30, 2020

CONTACT: Dr. Kathleen Boesze-Battaglia, Director of Honors Program, battagli@upenn.edu

FOR MORE INFORMATION: www.dental.upenn.edu/summerresearch CONTACT: Dr. Esra Sahingur, Associate Dean of Graduate Studies and Student Research, sahingur@upenn.edu

OTHER RESEARCH OPPORTUNITIES Learn more about research opportunities through these other programs via the website.

Leonard Davis Institute Summer Research Fellowship www.dental.upenn.edu/leonarddavisinstitute Dual-degree Programs www.dental.upenn.edu/dualdegree

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FACULTY Q&A DR. DANA GRAVES Vice Dean for Scholarship and Research Director, Doctor of Science in Dentistry Program Professor, Dept. of Periodontics BA in Chemistry, SUNY at Binghamton; DDS, Columbia University; Periodontology, Harvard University; DMSc in Oral Biology, Harvard University

What are your current research projects?

My research projects are driven by grants and I have three major projects in distinct areas. One of the projects involves the human oral microbiome, which is quite exciting, and I am very fortunate to work with Dr. Pat Corby in the Center for Clinical and Translational Research. The others involve different aspects of diabetes and use animal models. One is focused on periodontal disease. Periodontal disease is significantly affected by diabetes, and I am interested in the cellular dysregulation that occurs. Another project involves wound healing, which is also affected by diabetes.

What qualities do you admire or think are important in researchers?

I think researchers admire creativity, so having a creative solution to a difficult question is important. For example, you may want to prove something, but to do so effectively may require a creative approach; both the idea and approach to testing it require creativity.

There are many levels where creativity can be important.

The ability to interact with other people in an academic environment is very critical. You need to communicate with your lab members so they do the right things and understand the research process.

You have to communicate your results to other researchers and convince other people that what you are doing is useful. So, communication is a critical component of research.

I also admire the ability to remain calm and thoughtful when things do not go well, to deal with setbacks, and to take a logical approach to solving problems.

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What was the most difficult time in your research?

How did you get over it?

Setbacks happen frequently and there are various types. You have hypotheses which are incorrect, or in my case, I had a hypothesis that was generally correct but did not fit the specific situation. I had a hypothesis that a chemotactic factor would be critical for recruitment of monocytes in the formation of osteoclasts. The model I used was tooth eruption. It so happens that the hypothesis was true for most situations, but for tooth eruption, it was not true.

I used a genetically modified mouse which had a gene deletion of a chemotactic factor that recruited monocytes – but the deletion had no effect on tooth eruption. The chemotactic factor did not play a role in tooth eruption. However, it was important in most other situations where osteoclasts are formed. The setback was that I published a paper disproving the hypothesis in the tooth eruption model I was testing, so I lost funding for that particular project.

In another situation, there was a viral infection of the mouse colony so all the mice involved in the research projects were euthanized.

It cost over $100,000 to regain the mice that were lost and for one year all the projects stopped. We overcame this by studying tissue specimens from projects that had been done previously. Thus, we were able to continue producing results, collecting data, and writing papers, but not for the original project. We had to wait until the mice were re-derived. Things go wrong but can often can be overcome.

Any advice for students who are interested in research?

First of all, I think a research experience is very valuable from a very practical standpoint and secondly, it provides an opportunity to be a part of something that really is hard to find elsewhere. From a practical aspect, research is the most effective way to teach critical thinking. The enrichment aspect comes from the ability to test an idea or to examine something new. There are many rewards, including a sense of accomplishment, that come with participating in original research.

FACULTY Q&A DR. KATHLEEN BOESZEBATTAGLIA Professor, Dept. of Basic & Translational Sciences Research Honors Program Director

How can students go about finding a research project?

There is the summer research program and an honors program here at the School.

Penn does a very good job of making research accessible to students. If a student wants to do it, they certainly have many opportunities and labs to experience a research environment. I encourage anyone interested to participate in a research project at PDM. There is a new Associate Dean for Graduate Studies and Student Research who can help connect students with research projects, Dr. Esra Sahingur.

Research also enables you to develop critical thinking and interpretation of the literature. A dentist will be faced with new treatments, devices, and materials used in patient treatment. How do you evaluate them? Research teaches you how to examine and interpret data. There is no better way to learn how to critically evaluate the literature and to learn how to make decisions on whether a product or technique may be good for patients. I think a research experience has so many valuable components that if students do not take advantage of it, they will be missing something valuable. I also make a suggestion that students think about different careers that they can participate in, including careers that involve teaching or research, which are compatible with being a clinician. A dental student has many opportunities and many paths that they can take.

Currently, Dr. Battaglia’s lab is focused on understanding the molecular mechanism of age-related degenerative diseases by deciphering alterations in metabolism.

What qualities do you consider valuable in a researcher?

As a traditionally trained biochemist/biophysicist, I would have answered that researchers must develop highly qualitative assessments for basic processes. Over the years, my viewpoint has evolved with increased emphasis on understanding and developing viable therapeutics for disease processes. Overall, this requires a researcher who bridges basic concepts with clinical realties. Ultimately, some of the best researchers are both creative and think outside the box, and have the organization skills to persevere with well-designed studies.

What was the most difficult time in your research?

A research career is mostly characterized by both high and lows. Challenges do come in all forms; commitment to family, lack of infrastructure support, personnel struggles, and general difficulty in work life balance. Perhaps the most challenging for me was making time for my two daughters when they were young, and juggling the demands of scholarship for tenure. I had a 4-year-old at home and was pregnant with my second child my tenure year. There was no trick — just a lot of 5 a.m. mornings, kids and toys in my office, and evening mealtimes which I tried not to miss. As for research, it worked; I collaborated and have always enjoyed answering the question, “I wonder why it works that way.”

What advice do you have for students interested in research?

Pursue your passion, find a lab that has the type of work environment and project that you want to spend your non-existent “extra” time in. Some important things are to keep the balance — many experiments you think failed are really opening up a new line of study — look at the failures in that light. Rely on your basic common sense; it is good to ask yourself if what you are doing make sense. Is there a better way to do this particular experiment or a better way to test my hypothesis? Once in a lab group, find mentors.

Look at what these individuals do when they get stuck in their project, and see how they present their ideas.

“Ultimately, some of the best researchers are both creative and think outside the box, and have the organization skills to persevere with well-designed studies.”

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FACULTY Q&A DR. RICHARD DOTY Professor of Psychology in Otorhinolaryngology: Head and Neck Surgery Smell & Taste Center, University of Pennsylvania Medical Center B.S. in Psychology/Biology at Colorado State University; M.A. in Experimental Psychology: Psychophysics at California State University in Conjunction with National Aeronautics & Space Administration (NASA); Ph.D. in Comparative Psychology/Zoology at Michigan State University. Postdoctoral work in Behavioral Endocrinology at the University of California, Berkeley.

What is your current research project?

I have a number. Back in 1980 we were the first NIH-funded Smell and Taste Center in the United States. Our mission was research, patient care, and education. I’ve been with the Center since that time and its Director since 1990. We currently do a lot of research in the areas of neurology and neurodegenerative disease. We are particularly interested in the relationship of central brain cholinergic function and olfaction. Some of our past projects involved Alzheimer’s disease, and its connection to olfaction. Alzheimer’s, like Parkinson’s, is a disease in which smell loss can be a very early sign.

We also have research projects on taste. For example, Dane Kim (D’22) has completed a project on third molar extraction which will be submitted for publication soon. Such extraction can impact the lingual nerve of some people. His interesting finding is that persons in our clinic database, whose extraction occurred many years ago, actually are statistically more sensitive to tastes. Another taste area we have focused on involves sensitivity to the bitter taste of phenylthiocarbamide (PTC), of which about 70% of the population can perceive. So-called “bitter taste” receptors are actually found throughout the body, e.g., in the gut, brain, gonads, and pancreas, where they serve non-taste functions. Interestingly, tasters of PTC are less likely to contract rhinosinusitis, since they possess more “bitter” receptors in the nose that impact ciliary clearance and secretion of antibacterial agents, such as nitric oxide.

I think one of the things that we are best known for is the development of the University of Pennsylvania Smell Identification Test (UPSIT; commercially known as the Smell Identification Test).

This reliable quantitative “scratch and sniff” test has been translated into over 30 languages and is self-administered. The development of the test has resulted in massive amounts of research in aging and many diseases, including numerous neurodegenerative diseases, schizophrenia, and systemic disorders. It is gratifying to have developed the first and most widely used commercially practical smell test that has led to new avenues of understanding brain function.

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What qualities do you admire or think are important in researchers?

I think their desire to do high-quality research is high on the list. It’s a bit like Picasso. When he started he used to do little things and never got to the great masterpieces. So many of us go through a phase when we just propose things to do research on and that’s fine at certain stages of our careers, but I think, ultimately, it’s whether the research is novel enough to make a meaningful contribution.

The ideal, albeit rare, study is one that breaks or shifts a paradigm.

Those are the ideas that ultimately shape things. So in order to know what’s important to do, you need to know the field very well. Then you can put into perspective what the next steps should be. That’s a very important aspect of research and that comes with experience.

It’s very hard to judge a paper if you don’t know that field, or are not immersed in it or trained in it. You try to form interdisciplinary relationships with other scientists, because they know their fields and they typically don’t know your field. Collaboration is a big player. If you can meld specific skills of different groups to focus on a problem, then that’s ideal. Interdisciplinary research can shed in-depth knowledge on a problem. Hopefully what comes out are advances that will benefit all creatures on this planet, not just humans.

What was the most difficult time in your research?

How did you get over it?

Well sometimes success in research is not a given — you get an idea and you test it. Sometimes you’re right and sometimes you’re wrong.

Generally if you have enough experience, you’re more often right than wrong. But certainly there are times where you have an idea and you test it and it doesn’t turn out like you expect. At the same time, often you’re looking for one thing and by serendipity, discover something else. For example, when we developed the UPSIT we didn’t know what to expect and we were just excited about testing people. As it turns out, this simple test opened up new avenues of understanding. Because I’m not wedded to, or particularly trained,

in certain fields of medicine, I am open to trying crazy things. For example, we tested people with myasthenia gravis (MG), which is classically considered to be an autoimmune disorder and to not have a central nervous system association. We found that people with this disease have the same degree of smell loss as people with Alzheimer’s and Parkinson’s. We had a hard time getting that research published, but it was published and now has been replicated several times. Many people thought that this wasn’t possible.

Unfortunately, the field of olfaction has been underappreciated, almost mocked. You’re studying smell, what’s wrong with you? I guess we associate smell with bad things but this is clearly changing, at least in academia.

But in the case of MG, we discovered something that is very important and still needs to be followed up on. Our findings suggest that a central nervous system cholinergic deficit associated with smell loss is present in this disease. This and other observations have led to the hypothesis that smell function is affected in neurodegenerative diseases by central cholinergic circuits. It was fortunate that the test that I invented has been given to subjects suffering from well over 30 different kinds of neurodegenerative diseases. This has led to the idea that the different degrees of smell loss observed among such diseases may reflect differing degrees of damage to forebrain cholinergic circuits. Of course in Alzheimer’s, acetylcholine is a big player regarding memory problems, but acetylcholine is also a pretty big player in other diseases. However, there is a tendency, I think, for people to focus only on a single disease at a time and to miss common connections among diseases that may aid in understanding the underlying pathologies.

Any advice for students who are interested in research?

Not everyone is cut out for doing research, but to find out you must jump into the activity. It is key that students who have an interest find projects that truly fascinate them and they enjoy. Finding a mentor early in your career can be very helpful. I think there’s a sense that if you accomplish things in research, you’re educating a

larger audience by your publications. It is more than giving a lecture to a class — you’re giving a lecture to an entire world in a way. So when you publish your research findings, you’re having a major impact on others. It’s very fulfilling, but it can also be disappointing at times as there is a lot of grunt work in collecting and analyzing data. Eventually research funding must be sought and this can be a grueling experience.

You have to be able to accept rejection both in terms of grant submissions and publications. Like your first term paper, a lot of red marks can come back but you learn from such marks. Research is constantly dealing with acceptance and rejection. You can go through periods of not having grants and periods of having grants, and it’s great. Today, researchers have to be astute enough to write grants and you have to market their findings and ideas. I think that aspect of research is sometimes the most difficult.

I view research as a type of art. In visual art, for example, you choose your medium, whether it be clay, acrylics, or watercolor. In science, you do the same thing. You choose your topic, medium, and whatever tools are needed to produce the published product. The way you make your graphs, the way you communicate information — it’s all art. Art and science are intertwined because they have the same elements of creativity, execution, and all of the elements of harmony.

Getting back to advice to young people, I reiterate the need to expose yourself to a field and learn as much about it as you can.

You will then spot things — oh boy, it would be interesting to do this, no one seems to have done that. That forms the genesis of a career. Find somebody who’s doing something in an area that you are interested in — and that’s what graduate school is basically. You choose a mentor for your PhD thesis based upon what they study.

I had a lot of interests, but I ended up doing human psychophysics with NASA, subsequently doing animal research for my PhD, then continued animal research, and eventually got back into human work. I found animals fascinating because, for many, smell is their primary sensory modality. Do they think and dream in terms of smells? These are questions it would be nice to ask your dog.

“I think research is fun; it has to be fun. And I think there’s a sense that if you accomplish things in research, you’re educating and publishing it — it’s more than giving a lecture to a class, you’re giving a lecture to an entire world in a way. ”

VERNON BRIGHTMAN RESEARCH SOCIETY 11

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