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Glycoprotein-130 and Chitosan-Coated Nanoparticles: Two Keys to Bladder Cancer Treatment

Studies show that glycoprotein-130 may hold the key to bladder cancer treatment. Inhibition of this IL-6 cytokine receptor can reduce bladder cancer cell proliferation and tumor volume in mice, as shown in a study performed by Dr. Darryl Martin, an Associate Research Scientist working with Dr. Robert Weiss at Yale University in the Department of Urology.

In the search for bladder cancer targets, the Weiss lab found that the cytokine IL-6 was overexpressed in several bladder cancer cell lines. Unfortunately, inhibition of IL-6 expression did not alter cancer cell proliferation–but the scientists were not discouraged.  The IL-6 receptor is located at a central point between 3 important pathways involved in cancer regulation: JAK/STAT, PI3K/AKT and ERK/MAPK. Perhaps greater success would be found by studying the IL-6 receptor. Glycoprotein-130, or GP-130, is a critical component of the IL-6 receptor, important for activation of downstream targets stimulated by IL-6 binding.

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Courtesy of Tawara et al. (2011) Cancer Manag Res. E3: 177-89.

To begin, Martin evaluated GP-130 expression in human bladder cancer specimens by immunohistochemistry and found that levels of GP-130 protein were correlated to tumor grade. He also looked at GP-130 levels in cell lines derived from human bladder cancers. Cell lines from high grade tumors showed elevated GP-130, while a cell line from a low grade papillary tumor showed less protein as seen by Western blot.

Martin then began experiments knocking out GP-130 in vitro. siRNA for GP-130 caused a 60% decrease in cell viability and 50% reduced migration in the scratch assay. Crystal violet staining of cells showed a reduced number of cells. This showed promise for GP-130 as a target for bladder cancer treatment.

To explore the mechanism by which GP-130 regulates cell proliferation and viability, the effects of GP-130 knockdown on the PI3/STAT pathway were investigated. Western blots showed reduction of AKT by 20% and a 50% decrease in mTOR, suggesting that GP-130 indeed utilizes this pathway, but that others may be involved, as well.  ERK1/2 and other pathways are currently being explored.

In his final set of experiments, Martin evaluated the effectiveness of GP-130 inhibition in vivo. Heterotransplant tumors were formed by subcutaneous injection of UMUC3 bladder cancer cells in nude mice. Upon tumor formation, GP-130 siRNA encapsulated in chitosan-coated nanoparticles was injected into tumors. Martin and Weiss developed this delivery system in collaboration with Drs. W. Mark Saltzman and Jill Steinbach in the Department of Biomedical Engineering at Yale in an attempt to enhance the amount of siRNA delivered to the cancer site. By delivering siRNA within nanoparticles, its stability is increased, and lower doses are required. One issue with cancer treatments instilled in the bladder is that the drugs do not always penetrate the urothelial wall. The coating of chitosan, a mucoadhesive polysaccharide, allows greater penetration of this bladder permeability barrier.

When the tumors were observed following treatment, tumor volume was significantly decreased in the siRNA-treated mice compared to the control mice.  In addition, levels of the GP-130 protein were reduced, as well as those of the CK20 protein, a marker correlated with advanced tumor stage. The success of this experiment was a critical step for the advancement o f GP-130 as a bladder cancer target, as tests in animals are required before clinical trials may begin.

Future experiments will include injection of cancer cells into the bladder to create a model more similar to bladder cancer in humans. This would also allow Martin to evaluate the effectiveness of the chitosan nanoparticle to penetrate the urothelial wall, inhibit GP-130 expression, and tumor growth.

The anti-obesity drug Belviq® may be repurposed for treatment of cocaine abuse.

belviq

Image courtesy of stockimages and David Castillo Dominici at FreeDigitalPhotos.net.

Belviq®, an anti-obesity drug that acts on serotonin receptors in the brain, shows signs of dampening the rewarding and reinforcing effects of cocaine in rhesus macaques. Dr. Gregory Collins of the University of Texas Science Center at San Antonio and the South Texas Veterans Health Care System San Antonio is working with Dr. Charles France to determine if this drug could be safely repurposed for the treatment of cocaine addiction.

Belviq®, also known as lorcaserin, is an anti-obesity drug developed by Arena Pharmaceuticals that was approved by the FDA in 2013. It works by activating the serotonin receptor 5-HT2c in the brain hypothalamus to induce satiety. However, activation of the 5-HT2c receptor can also dampen dopaminergic neurotransmission, which has important implications for cocaine abuse. Cocaine leads to the increased release of dopamine in the brain, a neurotransmitter which activates the reward pathways of the brain. Drs. Collins, Lisa Gerak, and France are studying whether the activation of 5-HT2c receptors could counteract the increase in dopamine caused by cocaine, reducing the rewarding and reinforcing effects of the drug. “There have been a lot of preclinical studies looking at 2c receptor agonists and 2a receptor antagonists as phamacotherapies for cocaine abuse but since this one is actually in the clinic it should be pretty easy to repurpose it for a different indication if we can find effects in the lab,” stated Collins.

Drug repurposing, or the study of a drug currently used for one disease or condition for its use in other diseases, is a strategy which can speed the time it takes for a drug to travel from the lab to the clinic. By beginning with a drug which has already been proven safe for humans with one disease, the success rate is greatly increased for its use in another. The NIH National Center for Advancing Translational Sciences developed a program in 2012 to support drug repurposing, which can be read about here.

In order to repurpose lorcaserin, Collins needed to determine the effectiveness of the drug to reduce cocaine self-administration in animals, to confirm that the dose was still safe, and to determine that tolerance to lorcaserin didn’t develop. For his experiments, Collins used the rhesus macaque, a species of monkey with behavioral responses to cocaine very similar to that of humans.

In the first set of experiments, the possibility of negative behavioral effects was tested in monkeys. This allowed them to determine a safe and pharmacologically active range of lorcaserin doses. Importantly, they observed that lorcaserin treatment induced yawning in monkeys, a behavioral response that is characteristic of 5-HT2c activation, indicating that the scientists were maintaining receptor specificity with their treatment method.  They also evaluated the effects of lorcaserin on food-maintained responding, a test that was used to confirm that the changes in animal response to cocaine were actually due to the lorcaserin treatment, and not just a general disruption of the animals’ behavior. This test showed only modest changes in food-maintained responding, allowing Collins to proceed to testing the effects of lorcaserin against cocaine.

In the next phase of research, Collins and colleagues measured blood levels of lorcaserin in monkeys to determine the point at which lorcaserin is highest in the body following treatment. This information is important for identifying the appropriate pretreatment time to study the effects of lorcaserin against cocaine. In behavioral treatments, Collins was then able to treat the monkeys with cocaine at a point in which lorcaserin levels were highest.

Finally, the key experiment for lorcaserin was performed. Would treatment with the drug decrease the monkeys’ interest in cocaine? To determine this, Collins and colleagues used a cocaine self-administration assay in which the monkeys were trained to press a lever to self-inject cocaine. Normally, monkeys will respond at high rates to earn injections of cocaine. However, if the rewarding and reinforcing effects of the drug are reduced by lorcaserin, the monkeys should start to reduce this cocaine-taking behavior.

Amazingly, when the monkeys were pre-treated with lorcaserin, their preference for the lever delivering cocaine was significantly reduced. In fact, this effect was consistent over 14 days, suggesting that the monkeys did not develop a tolerance to lorcaserin. In addition, the effects of lorcaserin treatment were also observed with larger doses of cocaine, suggesting that the monkeys were unable to surmount the effects of lorcaserin by taking more cocaine.

This is excellent news for Dr. Collins and the France lab, suggesting great promise for lorcaserin in the treatment of cocaine abuse. As investigations of the anti-cocaine effects of lorcaserin move into human cocaine-abusers, Drs. Collins, Gerak, and France are now beginning to assess the effectiveness of lorcaserin against other stimulants of abuse such as methamphetamine.

To learn more about the France Lab, click here.

Reynold Spector Award in Clinical Pharmacology Lecture by Dr. Scott A. Waldman

Dr. Scott A. Waldman received the Reynold Spector Award in Clinical Pharmacology at this year’s national ASPET meeting at Experimental Biology. Dr. Waldman gave a presentation regarding his award-winning scientific achievements titled, “Bench-to-Bedside Translation in Clinical Pharmacology: From Knowledge Generation to Healthcare Delivery.” Dr. Waldman outlined the history of his research on the gastrointestinal receptor guanylyl cyclase C, or GCC, from the initial characterization of its overexpression in colorectal cancer to its use as a biomarker and therapeutic target for the disease.

Colorectal cancer is the 4th leading cause of cancer in the United States and the 2nd cause of cancer-related death. It is typically caused by the sequential accumulation of mutations that cause normal intestinal epithelial cells to transition to a hyperproliferative state, followed by the formation of adenoma and final progression to carcinoma.

Guanylyl cyclase C is a receptor localized to the intestine. The molecules which bind the GCC receptor include the hormones guanylin and uroguanylin. Interestingly, this receptor also mediates the symptoms of Traveler’s Diarrhea by binding to the enterotoxin released by harmful bacteria.

One theory behind the initiation of colorectal cancer is that of paracrine hormone insufficiency. The hormones guanylin and uroguanylin are the most commonly lost gene products in colorectal cancer. This reduction occurs during the early phases of cancer. When these hormones are lost, the receptor GCC is silenced. Studies have shown that loss of GCC results in an increased incidence of colorectal cancer in rodents, leading to its identification as a tumor suppressor. Therefore, Waldman hypothesized that hormonal replacement therapy could prevent the occurrence of colorectal cancer recurrence. By maintaining homeostatic levels of guanylin and uroguanylin, perhaps the silencing of the receptor could be avoided and carcinogenesis prevented. Fortuitously, since the GCC receptor is exposed to the lumen of the small intestine, hormone therapy can be delivered orally, making it amenable to clinical use. When tested in mice, hormone replacement therapy eliminated tumorigenesis. Currently, Dr. Waldman is collaborating with the NCI Division of Chemoprevention, Ironwood Pharmaceuticals, and the Mayo Clinic to test paracrine hormone replacement therapy in humans.

Dr. Waldman’s lab then investigated the use of GCC as a biomarker for colorectal cancer. GCC is only found in the small intestine and colorectum normally. However, they found that it can also be detected in colorectal cancer cells. Could GCC be used as a marker to test for colorectal cancer metastasis? Indeed, upon further research his lab proved that RT-PCR analysis of extraintestinal tissues can indicate the presence of metastatic cancer cells, as well as the harder to detect micrometastases. Dr. Waldman is also investigating the use of GCC as a biomarker to differentiate tumor stage and risk of recurrence. Currently, clinical trials are underway to determine whether chemotherapy, a treatment typically reserved for metastatic cancer, will be effective for patients who are not categorized with metastatic cancer by current staging guidelines, yet have extraintestinal sites of GCC-positive cells, indicating micrometastases.

The third area of research which Dr. Waldman has pursued is the development of GCC-based vaccines to prevent colorectal cancer recurrence. He hopes to direct the immune system to metastatic cells expressing GCC.  The mucosal and systemic systems have different lymphoid organs and separate effectors, providing a dual immune system with minimal cross talk. Waldman is taking advantage of this to immunize the systemic compartment against GCC-expressing cancer cells, without inducing a response in the mucosal compartment where GCC is normally localized. In fact, a vaccine containing GCC elicited antibody and killer T cell responses in mice, preventing metastatic tumor formation without creating or exacerbating inflammation. Currently, Dr. Waldman is testing a GCC-based vaccine in a Phase 1 trial of stage I and II colorectal cancer patients. So far, positive antibody and killer T-cell responses have been observed.

The advances in cancer research that Dr. Waldman has accomplished is the dream of many scientists. To discover the basic mechanisms of a disease and use that information to not only diagnose, but also treat the disease is a feat that few scientists ever accomplish, and Dr. Waldman is indeed worthy of the Reynold Spector Award in Clinical Pharmacology for his research. Throughout his presentation, Dr. Waldman also took the time to highlight scientists who have acted as mentors and friends, supporting him throughout his career. “I think it’s a rare opportunity that we get to thank our mentors in public,” Waldman said. “These are the people that set our feet on the path for our careers and shaped us… For me these are the people on whose shoulders I’m standing, trying to catch a brief glimpse of the horizon in the distance.”

During his doctoral training at Thomas Jefferson University, Dr. Waldman worked in the lab of Dr. Ken Chepenik.  “He is the one that instilled in me a love of science and research,” said Waldman. He also expressed appreciation for the friendship he has maintained with Dr. Chepenik through the years. “While he taught me many things scientifically, the more important gift that he gave me was his enduring friendship.”

In 1979, Dr. Waldman began a postdoctoral fellowship in the lab of Ferid Murad, co-winner of the 1998 Nobel Prize in Physiology or Medicine. “He taught me how to do big science,” stated Waldman. “The most important thing that he taught me was actually a passion for translational research. He is the quintessential physician-investigator. Every day it was, ‘What are we going to discover today that we can translate to better manage a patient tomorrow?’” In addition to the science he taught Waldman, their families have remained close friends for 35 years.

Dr. Waldman also thanked his colleague Dr. Andre Terzic, whom he met as a junior faculty member at Thomas Jefferson University. Waldman expressed gratitude for several lessons in personal and professional development. “There’s no ‘I’ in team,” said Waldman of advice gained from Dr. Terzic. “When you are working on something, you are doing it for the betterment of the institution and organization, not for the betterment of the individual. In every interaction, always take the high road, and I’ve tried to do this throughout my career.” Waldman and Terzic have produced a textbook together in basic and clinical pharmacology, and have been the co-editors of Clinical Pharmacology and Therapeutics for ten years. “While scientifically and professionally he’s given me a lot, more importantly he’s given me his friendship, which is of paramount importance,” said Waldman.

Lastly, but most importantly, Dr. Waldman credited his success to his loving family. “All the mentors and all the science is great, but at the end of the day there’s got to be something that inspires you. My inspiration, the thing that gets me up every day, is my family,” said Waldman. “Of all the things that I’ve ever done, of all the cool science that I’ve done and the projects that I’ve been a part of and the people who I’ve met, it’s all wonderful, but truly my family is probably the most important thing I’ll ever do in my life.”

The Reynold Spector Award in Clinical Pharmacology was established in 2014 by ASPET in recognition of Dr. Spector’s dedication and contributions to clinical pharmacology. The award recognizes excellence in research and/or teaching in clinical pharmacology. This award is made possible by an endowment to ASPET from Dr. Reynold and Mrs. Michiko Spector.

Is Optogenetics Too Good to Be True?

Optogenetic Light Alters Gene Expression in Wild-type Microglia

New research indicates that the use of optogenetic light for cell-selective control may have effects on surrounding cells, an important consideration for the use of this recently popularized neuroscience technique. Kevin Cheng, a graduate student in the lab of Dr. Jyoti Watters at the University of Wisconsin-Madison discovered this phenomenon while performing research with microglia.

For those unfamiliar with optogenetics, this technique utilizes the ability of light-responsive proteins to control cells. By targeting these transporters to certain cells, scientists can activate cells of their choosing by exposure to blue and other wavelengths of light. This also allows cells to be turned on and off at the researcher’s choosing. This technique was originally used to excite or inhibit neurons, though it has now expanded to various cell types and can also be used to control other functions of the cell such as GPCR activity.

To learn more about the basics of optogenetics and why it is so cool, check out this clip by Nature Video

Originally, Cheng was trying to transduce microglia cells with the construct for the light-responsive protein. They expected that optogenetic light would alter gene expression in the optogenetic protein-containing cells without effects on the wild-type cells lacking the light-responsive transporter. However, what they found was very different. When exposed to the light, control microglia lacking the light-responsive protein showed changes in gene expression. “The first time that I brought this to our weekly lab meeting, they laughed. Do you think it is possible that this is happening?” asked Cheng. “And they said no, it’s not.” After rigorous experimentation, Cheng was able to prove to his labmates that indeed, there were side effects of optogenetic exposure in normal cells.

To prove his hypothesis, Cheng utilized a black-walled 96-well plate aligned with an LED array. This setup allows for control of light duration and intensity in each well. Microglia were grown on the plate, then exposed to blue light at 450 nm, a common wavelength used for optogenetic experiments. Following exposure, pro-inflammatory gene expression was determined by quantitative RT-PCR.

Since the inflammatory response within the central nervous system is mediated by activated microglia, Cheng compared gene expression in both basal and LPS-activated microglia. He also evaluated the difference between a single bolus of light and a light pattern commonly used in optogenetics.

Of the pro-inflammatory genes measured, COX-2 expression was induced in basal cells exposed to both bolus and optogenetic light patterns. In LPS-activated cells, the genes IL-1b, iNOS, COX-2, IL-10, IL-6, and VEGF were decreased and IGF-1 was increased after bolus light exposure. Further, IL-1b, iNOS, COX-2, and IL-10 also exhibited decreases in gene expression following light with LPS activation. To make sure the energy dose delivered was not harmful to the cells Cheng also measured the potential for blue light to induce cell death and DNA damage in microglia, and found no effect. This suggests that wild-type microglia respond to blue light and that it may exert a surprisingly anti-inflammatory effect.It also demonstrates that optogenetic patterened light exposure can have effects on wild-type cells near the cells of interest.

To date, this is the first report of non-specific effects of optogenetic light. This study has important implications on the field of optogenetics, a technique which has named “Method of the Year” in 2010 by Nature Methods. Cheng plans to expand his experiments to include other cell types and to explore the mechanism behind this unexpected phenomenon.

For the abstract of this work, visit here.

To learn more about research in the Watters Lab, click here.

New Tamoxifen Analog Reduces Amphetamine Neurochemical and Behavioral Effects

Colleen Carpenter

Colleen Carpenter

Amphetamines are the second most abused drug worldwide, but no effective treatments are available for amphetamine abuse. At this year’s Experimental Biology meeting, graduate student Colleen Carpenter from the University of Michigan presented data revealing that the chemotherapy agent tamoxifen can serve as a platform for the creation of a pharmacological treatment against amphetamine abuse.

Currently, the mainstay of amphetamine abuse treatment is psychotherapy. “The problem with behavioral treatment methods is that they are not very effective,” Carpenter said. “We’re looking at a pharmacological way to block amphetamine abuse.” In the lab of Dr. Margaret Gnegy at the University of Michigan Department of Pharmacology, Carpenter is looking for pharmacological treatments to inhibit the rewarding and reinforcing effects of amphetamine.

The effects of amphetamine are caused by the release of the neurotransmitter dopamine into the synapse via the dopamine transporter in the brain. “People have actually tried to target the dopamine transporter directly,” says Carpenter. “The problem is, many ligands that bind to the dopamine transporter act as dopamine uptake blockers. Blocking uptake of dopamine is bad, because that’s how cocaine works. We still have the increase in extracellular dopamine at the synapse which has its own reward functions.” The Gnegy lab is taking an alternative approach. Rather than targeting the dopamine transporter, they are now looking at the upstream regulator of the dopamine transporter, protein kinase C.

It is known that amphetamine activates protein kinase C, or PKC, which ultimately enhances the release of dopamine through the dopamine transporter. By modulating the activity of PKC, perhaps dopamine release could be reduced, decreasing the rewarding and reinforcing effects of amphetamine.

There are numerous available inhibitors of PKC but the selective estrogen receptor modulator tamoxifen is the only PKC inhibitor known to cross the blood-brain barrier.   Tamoxifen acts at a regulatory subunit of PKC, so it causes less problems than one that acts at the active site.

At this year’s ASPET meeting, Carpenter reveals recent data suggesting that a compound modeled after tamoxifen called C091, designed and synthesized by the Vahlteich Medicinal Chemistry Core at the University of Michigan, is able to reduce PKC activity and dopamine release without affecting the estrogen receptor at relevant concentrations. In addition, behavioral studies with the new compound showed significant decreases in amphetamine-related behavior in mice.

First, Carpenter determined that C091 is a better inhibitor of PKC activity than tamoxifen, as indicated by changes in the ability of PKC to phosphorylate specific protein targets when treated with C091 versus tamoxifen.

She then investigated the potential for C091 to bind estrogen receptors, as this nonspecific binding could cause unwanted side effects if C091 is purposed as a therapeutic against amphetamine abuse. To determine this, she performed an estrogen receptor competitive binding assay. When compared with estradiol and tamoxifen, C091 did not bind to the estrogen receptor at concentrations where it effectively inhibited PKC.

To determine changes in actual dopamine release at the synapse, Carpenter measured the levels of dopamine release induced by amphetamine with and without treatment with various doses of C091. In order to measure dopamine release in vitro, the ends of dopamine transporter-expressing nerve terminals from the striatum are pinched off to form small spheres called synaptosomes. These small spheres are able to respond to amphetamine exposure and secrete dopamine via the dopamine transporter. A suprafusion system is used to collect the dopamine released from the synaptosomes. In short, this system allows the controlled perfusion of drug solutions over the synaptosomes and the dopamine-containing eluent is collected in fractions for quantification. Treatment with amphetamine stimulated dopamine release from striatal synaptosomes. However, dopamine efflux was reduced with increasing doses of C091.

After proving that C091 inhibits PKC activity and reduces dopamine release, Carpenter moved on to a critical experiment: would C091 have actual effects on amphetamine- induced behavior in an animal? For this experiment, mice were pretreated with C091 followed by amphetamine treatment, and changes in locomotion were observed. Normally, amphetamine exposure significantly increases mouse locomotion due to its action in the brain. When mice were treated with C091 systemically prior to amphetamine, their locomotion was greatly reduced.

Future studies with C091 will include a model in which the effects of C091 on amphetamine self-administration can be determined, as well as microdialysis for measurement of dopamine levels in vivo.

To read more about the research performed in the Gnegy lab, click here.

For more information about the creation of tamoxifen analogs, check out

de Medina, P., Favre, G. & Poirot, M. Multiple targeting by the antitumor drug tamoxifen: a structure-activity study. Current medicinal chemistry. Anti-cancer agents 4, 491-508 (2004).

Why Undergraduates Should Attend EB

This week at Experimental Biology, I had the pleasure of meeting several talented undergraduates attending the meeting with their advisors. These students were participants of the Summer Undergraduate Research Fellow (SURF) program led by ASPET and received travel awards to attend the meeting. Others were selected to participate in the ASPET Best Abstract Competition due to their outstanding research. As I interviewed these students and their faculty, I realized that the students attending this conference represent the best undergraduate researchers across the United States. While graduate students, postdocs and faculty may have resources to fund travel to meetings, few undergraduates receive that opportunity. Their attendance at this meeting is a testament to their hard work, intelligence, and commitment to research. As an undergraduate, I went on a road trip with my advisors to a national meeting in Chicago. That experience had a profound impact on my view of science and career goals. I also gained valuable connections at the meeting that have benefited me through the years. I believe that many scientists find their passion for research rekindled at national meetings. Imagine what the impact it must have on students new to science.

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Joshua Sheetz and Alexandra Van Hall

Caitlin Caperton

Caitlin Caperton

Senior Joshua Sheetz is majoring in Biochemistry and Biophysics at the University of North Carolina-Chapel Hill, and worked in the lab of Dr. Henrik Dohlman from the Department of Pharmacology in the SURF program. Sheetz received a travel award this year through SURF to attend Experimental Biology. When asked why he wanted to attend EB, he said he was excited about, “being able to gain experience talking about my research and hearing leaders in the field speak throughout the week.” He is planning to begin his graduate studies in Pharmacology at Yale University this fall. Sheetz is interested in meeting other students to learn about the grad school experience, as well as tips for the application process. Dr. Dohlman is happy to have Joshua join him at EB. “His lab experience represents a tiny fraction of experimental pharmacology. It is important to be exposed to other questions and approaches. It will help in finding a question they can be passionate about, and also introduce them to new approaches that may be common in one field but not another. New approaches lead to new discoveries,” he said. He encourages his students to attend the keynote lectures while at Experimental Biology. “It may be only opportunity they get to hear such prominent scientists speak about their work.”

Alexandra Van Hall is a junior Chemistry major at the University at Buffalo who received a SURF travel award with Dr. Margarita Dubocovich in the Department of Pharmacology and Toxicology. “I’m just excited for the poster sessions. This is my first big conference that I’ve been able to come to,” Van Hall said. “I want to go into academia, so I really want to get a feel of what these meetings are like.” Advisor Dr. Dubocovich encourages her students to attend national meetings such as Experimental Biology. “We have to show them how much fun in some ways it is to do scientific research and what a privilege we have. I was very privileged to attend many meetings and network and meet leaders in pharmacology as a junior scientist.” She hopes that her undergraduates will be able to network, meet people, and observe the recognition of good research and hard work at Experimental Biology.

Bao Vi Vo, a senior at Carroll University, performed research through the SURF program at The Medical College of Wisconsin in the lab of Dr. John Imig. This is her first time at Experimental Biology, and she plans to attend graduate school in Pharmacology. “I presented my poster here, so I got excited to talk about my research with other people. When I went to the meeting I met many other people from different places,” she said. Dr. Imig supports undergraduates at national meetings because he likes them, “to come to meetings, get experience, especially if they want to go on to grad school to kind of get the experience of what it’s like.” He also noted that, “they have to see what it’s like and you get excitement from these meetings.”

Senior Neuroscience major Sneha Gupta from Washington and Jefferson College won the ASPET Student/Postdoc Best Abstract award for the undergraduate division of Behavioral Pharmacology, presenting her research with Dr. Katie Davis of the Johns Hopkins Medicine Department of Psychiatry and Behavioral Sciences. She has greatly enjoyed attending sessions on prions and the effects of aging on the brain, two areas of special interest to her. Dr. Davis wants her own students to have more opportunities to attend national meetings than she did as a student. She hopes that they gain more neuroscience experience and learn about behavioral pharmacology from other scientists during their time at Experimental Biology.

Caitlin Caperton, SURF participant and second place winner of the undergraduate Behavioral Pharmacology division of this year’s ASPET Student/Postdoc Best Abstract Competition, is a senior Psychology major at University of Arkansas-Little Rock. She performed research in the lab of Dr. William Fantegrossi in the Department of Pharmacology and Toxicology at the University of Arkansas for Medical Sciences. This is Caitlin’s first time attending a national conference. “I think it was a great opportunity just to learn about the process of coming to a meeting like this, like writing the abstract and putting together a poster and being able to present the poster. I think it was also good to learn about networking. I just attended the graduate student and postdoc colloquium and learned about how important that is,” she said. Caperton plans to attend graduate school after college. “I was at a meeting when I met the people in the labs I wanted to join for grad school,” said Dr. Fantegrossi. “It was very important for my applications.” Dr. Fantegrossi believes that the relationships gained at national meetings are especially valuable for undergraduates, and he makes sure his students attend the various networking sessions available at Experimental Biology.

Anna Scandinaro is a senior Biochemistry student from West Virginia University studying in the lab of Dr. Rae Matsumoto, and attending a national meeting for the first time. “It’s great to be a part of something like this where you can practice speaking in front of other people. That experience is wonderful and it’s going to help in any aspect of my life. I really enjoy people questioning me. It’s just great to be here with people from all over,” she said. Her graduate advisor Linda Nguyen attended the meeting with Scandinaro, and also supports undergraduate attendance at these meetings. “For undergrads it is daunting, it’s huge, if they don’t have someone already there guiding them through the meeting they might not be able to get out as much,” says Nguyen. “But I think the exposure to these various fields of science is a good experience.”

Sophomore Natalie Arabian participated in SURF research in the lab of Dr. Daryl Davies at the University of Southern California School of Pharmacy and presented her findings at the Student/Postdoc Best Abstract Competition, where she won the undergraduate award for Drug Discovery and Development. She plans to pursue a PhD following her undergraduate degree. “I definitely think it’s really important for undergrads to come to meetings and I think it’s really important for undergrads to know or at least have a good idea about what they want to study before they go to grad school,” she commented.

Another participant of the ASPET Student/Postdoc Best Abstract Competition was Emily Warner, a junior majoring in Neuroscience at the University of New England. She presented data from her research with Dr. Glenn Stevenson of the Department of Behavioral Pharmacology. “I definitely want to look for things that are going to gear our research in the future to look at where we are going to go next,” she said. Dr. Stevenson agreed with her thoughts, adding that Warner’s high involvement in research at his lab makes a meeting like this a much more fulfilling experience. “The utility of the meeting depends on the degree of immersion they get in the lab. If they are really immersed in the lab setting then I think this meeting might have some meaning for them,” he said. Dr. Stevenson also stated the importance of undergraduate attendance at national meetings for their future careers. “I’m all about getting them to the next level,” Dr. Stevenson commented. “And the best part is they take it seriously.”

Learn more about undergraduate research opportunities with ASPET here.

What Does Industry Want From You?

Lawrence Carter, Senior Director of Clinical Development at Jazz Pharmaceuticals, spoke at the ASPET Graduate Student-Postdoctoral Colloquium: How to Get Started on Saturday afternoon. The session was filled with talented scientists in careers from academia, industry, and the government sector. I had the pleasure of interviewing Dr. Carter and learned how his career has led to his current position at Jazz Pharmaceuticals, advice on ways to find positions in industry, as well as advice from his presentation on how to land a job in industry.
Dr. Carter received his undergraduate degree in Biology and Psychology at Kalamazoo College, and was himself a participant in the SURF program at the University of Texas Health Science Center in San Antonio (UTHSCSA). Through his undergraduate research experience, he was exposed to the field of behavioral pharmacology and joined the Pharmacology graduate program at UTHSCSA. Dr. Carter then completed a postdoc at Johns Hopkins University in which he performed human behavioral pharmacology research. Following his postdoctoral fellowship, he joined Jazz Pharmaceuticals as a Medical Science Liaison. Since then, he joined the faculty in the Department of Psychiatry and the Department of Pharmacology & Toxicology at the University of Arkansas for Medical Sciences and he maintains an adjunct position in the Pharm & Tox department at UAMS.

What does a Medical Science Liaison do?
In his previous position as Medical Science Liaison, Dr. Carter acted as the communicator between Jazz Pharmaceuticals and academic institutions and clinicians, as well as a resource for grant review and potential collaborations. “The MSL position is sort of like a field based scientist position,” he said. “You’re kind of the go between the inside of the company and the external face of the company for academic institutions and clinicians. You’re answering questions that are more scientific in nature than commercial in nature and you’re collaborating with folks,” he commented. Dr. Carter also interacts with scientists to learn about the cutting edge of the field and to tap into that expertise to benefit the company. In reverse, researchers communicate with the company though the Medical Science Liaison. “You might approach the company, saying, ‘Hey I’ve got this question about the drug that the sales rep can’t answer. I want to talk to a scientist.” When researchers are interested in doing some type of research with the drug, they would talk with Dr. Carter about potential research projects.
How does one find industry positions in their specific field of research?
• Review scientific literature for use of FDA-approved drugs, and find out who sells them
• Visit http://www.clinicaltrials.gov to determine who is performing clinical research in your field
• The Drug Information Association (DIA) conference is a prominent industry conference
• Keep up to date with companies by reading the industry and biotech news
• Review currently available job postings

Working with Pharmaceutical Companies: What does Industry Want from You?
Dr. Carter’s talk focused on the steps that trainees can take to become attractive candidates for industry careers and on several valuable resources to utilize along the way.
1. Become so good they can’t ignore you.
Attain expertise in at least one area. This will enhance your career capital, and open you to new opportunities. Dr. Carter added that people like to do things they are good at. He also recommended the following books as guides on your path to excellence.

Mastery by Robert Green

http://www.amazon.com/Mastery-Robert-Greene/dp/0670024961/ref=tmm_hrd_swatch_0?_encoding=UTF8&sr=&qid=

This book offers hard truths about the steps towards mastery of any skill. It discusses the following lessons:
• Value learning over money
• Expand your horizons
• Revert toward a feeling of inferiority (not to assume that you are the expert)
• Trust the process
• Move towards resistance and pain
• Apprentice yourself in failure
• Appreciate the how behind the what
• Advance through trial and error
How to Fail at Almost Everything and Still Win Big by Scott Adams

http://www.amazon.com/How-Fail-Almost-Everything-Still/dp/1591846919/ref=tmm_hrd_swatch_0?_encoding=UTF8&sr=&qid=

In this book by Dilbert comic author Scott Adams, the mastery of a few choice skills is also emphasized. Two important points from the book are that every skill you acquire doubles your odds of success and that the more you know, the more you can know.
2. Focus your efforts on strategic opportunities for you.
Playing to Win: How Strategy Really Works by A.G. Lafley and Roger L. Martin

Playing to Win: How Strategy Really Works

Playing to Win: How Strategy Really Works

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In “Playing to Win,” Lafley and Martin challenge readers to redefine their definition of strategy and winning in business. They ask the following questions:
• What is winning?
• Where are you going to play?
• How are you going to win?
• What capabilities and qualities must you have?

These questions may be used when considering jobs in industry. First, what do you want to do in industry? Bench research, regulation, or commercialization, for example? Next, where do you want to work? What type of schedule would you like? Industry is not monolithic– there are companies of various sizes and stages of development. Some companies are focused in a specific field of research. Based on what you want to do, find a company with a strong fit. Once you have chosen a few companies of interest, determine a strategy for finding jobs by carefully choosing with whom you choose to network, and learn how best to prepare for interviews in that position. Last, when considering positions from which to apply, use the job advertisement to establish what capabilities and qualities you must have to achieve this position.
3. Learn to be a good salesperson (of yourself).
Guerilla Tactics for Getting the Legal Job of Your Dreams by Kimm Alayne Walton, J.D.

Guerrilla Tactics for Getting the Legal Job of Your Dreams, 2nd Edition (English and English Edition)

Guerrilla Tactics for Getting the Legal Job of Your Dreams, 2nd Edition (English and English Edition)

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While aimed towards law, this book is a good resource for someone seeking a new job. In fact, they offer a money-back guarantee and this book is one Dr. Carter goes to when he prepares for job interviews. It offers several valuable suggestions that are applicable to many careers.
• Know everything you can about your employer and your interviewers
• Create your infomercial. Take the requirements in the job posting and match them to your top accomplishments. For example, this could be phrased by, “I have this job related skill you are looking for as evidenced by the following accomplishments on my CV.” If the job posting requires someone with excellent communication skills, state, “I have excellent communication skills, as evidenced by the awards that I have gotten for my teaching and for the invited presentations that I have been asked to give.” Select 3-5 of these required skills to insert into your conversations, and make sure that you get them across by the end of the interview.
• Develop and polish your “Miss Americas.” You rarely see a Miss America candidate stumble over the questions she is asked, as she has rehearsed her responses to these questions previously. For your job interview, perfect your elevator pitch and review likely interview questions. If there is anything that can be perceived as negative on your CV, know how to put a positive spin on it so that you may address it when it comes up.

Bonus Book Recommendation:
Power Questions: Build Relationships, Win New Business, and Influence Others by Andrew Sobel and Jerold Panas

Power Questions: Build Relationships, Win New Business, and Influence Others

Power Questions: Build Relationships, Win New Business, and Influence Others

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“What did FDR, Socrates, Shakespeare and Jesus have in common? According to Sobel and Panas, they all knew how to ask “power questions.” Read this book, and you will too!”
– Marshall Goldsmith, author of the New York Times bestsellers MOJO and What Got You Here Won’t Get You There

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