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Credits: Duke DIBS

Dr. Amir Rezvani is a professor of Psychiatry and Behavioral Sciences and Associate Director of Addiction Division at Duke University in addition to being one of the PI in the lab that I am working in this summer. One of the first things I noticed about him when I met him was his amazing sense of humor, which makes working in his lab joyful. He is definitely not the stereotypical scientist that we all imagine in our heads; one that never smiles or jokes, and is about science 24/7. In fact, he is quite the opposite. This week I decided to give him a short interview so I can learn more about him and his journey in the scientific world.

Dr. Rezvani was born in Persia (Iran) where he did his undergraduate at the prestigious University of Tehran which is the best and oldest university in the Middle East. He received his undergraduate degree in biology then got his masters in teaching biology. Although he was accepted in medical school and even put down a deposit for his tuition so that his spot could be saved, at the end he decided to go into biology instead of going to medical school. When I asked him why he chose to give up medicine to be a scientist, he replied that his high school science teacher was the main force in convincing him to pursue biology and the life sciences. That teacher had so much passion for the life sciences that became contagious that Dr. Rezvani caught it. After high school, he decided that he wanted a more science-based career so he gave up medicine to pursue something he loved more.

For graduate school, he came to the United States and landed in Missouri where he received another Master degree in Physiology. As if he didn’t have enough degrees, Amir Rezvani became Dr. Amir Rezvani, receiving a Ph.D. in Neurophysiology from the University of Illinois at Urbana- Champaign. He said he was drawn to neurophysiology because there was so much unknown in the field and there were great opportunities for discoveries. He was also interested in human behavior and neurophysiology encompassed that. At that time, his research looked at the effects of beta endorphins, a newly discovered endogenous peptide, on temperature regulation in rabbits. He then went to University of North Carolina at Chapel Hill for his postdoc (which explains his loyalty to UNC). After finishing his postdoc, he was recruited as a faculty in the department of Psychiatry at UNC where he became interested in addiction to alcohol by using alcohol drinking rats and monkey. In 1999, he finally came to Duke University and began working with Dr. Edward Levin. However, his unfaltering loyalty to UNC did not change (even though he is working at Duke which is kind of like enemy territory for him).

His advice for budding scientist is to be curious as much as you can about everything and read as much as you can. Read literature and then talk to other scientists, expose yourself to other scientists by going to talks and seminars and meetings and conferences. Doing all of this will help you find what you really love and what excites you. At the end of the day, you have to love it. Because you don’t want to wake up in the morning and hate what you’re doing. Life is too short for that. And last but not least, you need to be passionate about helping other people especially for medicine but also for science. Because every addition to the human knowledge, no matter how small, can eventually help someone somewhere in the world.

As you can see, Dr. Rezvani has lived a very dynamic and science-filled life, always ready to learn more. One can learn a lot from his life and experiences. I think the thing that I learned from listening to him is to always be prepared to learn (because he wouldn’t have collected so many degrees if he didn’t like learning) and to not be afraid to go against the tide and do things that you really enjoy. This lesson not only applies to budding physician/scientists like me but also everyone in the world.

Randomly self-assembling copolymers have repeatedly demonstrated great promise toward eliciting therapeutic immune responses, and specifically for autoimmune diseases. However, their mechanisms of action are not yet fully understood. Many factors such as pH and temperature can affect the nature of the self-assembly of copolymers thus influencing immunogenicity. We tested the hypothesis that factors such as pH and temperature can be manipulated to optimize the self-assembly of copolymers thus eliciting a more desirable immune response through shifting the nature of the T-cell response. This was implemented by analyzing the effect of pH, temperature, and sonication on the stability of the copolymers dissolved in solution. According to our results, increasing heat and pH were the most effective methods to optimize the formation of fibers. We next plan to use these copolymer solutions to vaccinate mice and use methods like ELISA to analyze the nature of their immune responses. This will help us gain a better understanding of the ideal steps to be taken to increase the solubility of these copolymers while simultaneously optimizing their immunomodulatory actions. Through exploring different methods to increase the solubility of copolymers in solution, we can work to better understand how to optimize the immunogenicity of copolymers in vaccinations.

This is a first draft of my abstract

Ecologic Factors Influencing Hormone Concentrations in Female Baboons

Although studies have shown how ecologic factors influence human female hormone concentrations and male baboon hormone concentrations, little is known about how these same factors effect female baboon hormone concentrations. This study measures correlations between estrogen, progesterone, and glucocorticoid levels and rank, weather, parity, age in the female yellow baboon population in Kenya’s Amboseli National Park. To determine the hormone concentrations, each fecal sample collected in Kenya was purified into a serum. Radioimmunoassays were then run on each sample, and hormone concentrations were correlated with field data on the individual the sample was from, time of sample, rank, and temperature. Although we do not yet have results, our hypothesis is that female baboon hormone concentrations and female human hormone concentrations will be similarly affected by parity and age, and that weather will effect both male and female baboon hormone concentrations similarly. Rank in female baboons is matrilineal, that is, a daughter baboon will be lower in rank than her mother suggesting that rank and hormone concentrations would not be correlated.

My abstract draft:

Will they learn to court? 
Studying the role of Or47b in drosophila courtship learning behavior

Behaviors are made up of both innate and plastic components and courtship is no exception. It has been discovered that courtship can be learned in drosophila melanogaster (fruit flies), given that the innate component is absent. However, we do not know the exact mechanism that enables this learning. In this study, we are focusing on the olfactory system because we hypothesize that olfaction is important in learning; more specifically that Or47b is a key olfactory receptor neuron that regulates the learning of courtship behavior. To do this, we are using fru mutant fruit flies and fru and Or47b double mutant fruit flies and group housing them with other males or females for a few days and then observing their courtship behavior. We are currently waiting for results, however if our hypothesis is correct, we expect the double mutant fruit flies to not court even after group housing them. These results could better our understanding of the mechanisms driving behavior changes in general.

First off, I want to thank everyone for doing such a great job presenting their chalk talk last week. I know that public speaking is a struggle for me and I’m sure I’m not alone. Everyone did a wonderful job and is on their way to becoming a great scientist!

A highlight of the chalk talk series for me was getting to see my roommate Georgia convey her science. Georgia has become a good friend of mine throughout the program, but I haven’t been able to talk to her about her project as much as I would’ve liked. Her talk was a great example of basic science and how scientists are working across the world to learn more about various organisms. Georgia’s lab studies baboons from Kenya and then analyses their fecal matter all the way in Durham, North Carolina. They then work to correlate the organism’s biochemistry with their behavior and ecological conditions in Kenya. I find it fascinating that something as natural as heavy rain can increase the level of glucocorticoids in a baboon’s system. I think that often there is a large gap in the minds of scientists between organismal activity at the molecular level and then at the level of the entire organism, but Georgia’s research does a nice job of bridging that gap to show how significantly an organism’s biochemistry can change as a result of something in their environment. This type of research is unfortunately often overlooked compared to research that has direct biomedical applications, and with the current political climate could face challenges with funding. I think Georgia did a great job of explaining why her research is good science, interesting, and deserving of public support.

I loved listening to everyone’s chalk talks this week, especially because we got to learn much more than just a sentence or two about everyone’s project. The project I decided to reflect on this week was Rebecca’s!

Rebeca’s project focused on the effect of an olfactory gene (or47B) in fruit fly courtship. She explained the behavioral aspects of fruit flies that was interesting and a seemed a little silly. We got to better understand the role of the olfactory genes and the fruitless gene that seems to be tied to courtship which was cool! I found Rebecca’s talk interesting because in my neuroscience class last semester we talked vaguely about olfactory genes and pheromones but didn’t speak much about it since pheromones occur mostly in other animals.

I’m interested to see how the rest of her fruit fly watching goes for the rest of the summer, and if the fruit/or47b mutant will not learn the expected courtship behavior of the fruit fly!

Nice job to everyone with their talks this past week!

The impending doom of an alarm clock waking me up from my nightly hibernation is less terrible when I know I have lab to look forward to (needless to say I’m not a morning person). Usually three snoozes later my day will start around 8:15. I’ll gather my things and make the arduous trek up the Edens stairs to my happy place: Joe Van Gough. The heroes of JVG will provide me with my elixir of life and I’ll finally start to come out of my hibernation.

Walking into lab (full of coffee, of course) is always incredibly exciting. I’ll never fully know what the day entails, but I know I’ll always get to learn something. For the past ten days we’ve been doing the social defeat experiment at 11 AM. I’ll spend my morning getting to hold cute little mice. I’ve been known to name them, cuddle them, and maybe drop a few ‘I love you’s if I’m feeling extra perky. I get to do science while spending time with animals and some great lab members. After the experiment is over, we usually break for lunch. I’ll hike my way to West Union and battle my way through 12 year olds to get food.

Back in lab, I’ll see what other lab members are doing and see if they need help. My official work for the day is over, but my lab usually needs help doing histology. We implant electrodes into the brains of the mice before our social defeat experiments to get data about activity in certain brain regions involved with depressive-like symptoms. To validate our data we must look at the brains after the experiment to make sure the electrodes we implanted were in the right brain region. That way we can support that our results show data from the region that we intended to be recording. I love this portion of the day because I get to see the project I’m currently working on come full circle. There’s always more histology to work on so I get to learn something new every day.

After my histology is done I make the walk back to Edens and spend my night finishing a paper for lab. I’m extremely grateful that I get to work every week with such talented lab members and have the privilege of learning from them. Not many undergrads get to learn so much so early and truly experience what life in a lab is like.

Ever heard of the Philadelphia chromosome? How about imatinib or Gleevec, the highly successful miracle drug most famously used to treat CML (chronic myelogenous leukemia)?

If so, you may have heard of my lab’s focus: the Abl family of protein tyrosine kinases.

When I searched through labs in the Department of Pharmacology and Cancer Biology and came across one with the focus of researching the functions the Abl family of tyrosine kinases, the faintly familiar ideas of the Philadelphia chromosome and Gleevec, which I had associated with the Abl gene, caught my attention. The Philadelphia chromosome represents the abnormal translocation in chromosome 22 found in leukemia cancer cells that results in the Bcr-Abl fusion gene. Imatinib, a chemotherapy medication, hinders the Bcr-Abl tyrosine kinase. Thus, I knew that research in the Pendergast lab, which centers on the exploration of Abl kinases, was sure to be interesting.

Each lab member has an individual project that stems from the Abl kinase focus of the Pendergast lab. Several lab members are utilizing mouse models for their projects. Others, actually all members minus me, continually learn and incorporate creative, new techniques to advance their projects. As for me, I am also learning many new techniques, but ones that have been around for much longer… Nevertheless, I am very grateful to my two lab mentors for taking time off of their own individual research projects to guide me and provide me with the tools I need to conduct research in this lab.

My research project builds on the project of the previous undergrad student in the Pendergast lab, who graduated in May. She focused on triple-negative breast cancer cells, in particular. The goal of my project is to define what role Abl kinases have in the signaling of a specific type of receptor tyrosine kinase (protein) in breast and lung cancer cells. Specifically, I am looking into the role of the interaction between Abl kinases and this particular protein in factors such as cell growth, EMT (epithelial-mesenchymal transition), migration, and invasion.

Now, you may be wondering what exactly is a tyrosine kinase? I will start by explaining one of the roles of phosphate groups. When transferred to a specific protein, a phosphate group can activate that protein. Enzymes (proteins) that add phosphate groups to other molecules, thereby activating the molecules, are called kinases. Tyrosine kinases are a subclass of protein kinases in that they possess the amino acid, tyrosine, to which the phosphate group attaches. Abl genes encode protein tyrosine kinases that activate proteins that are involved in factors such as cell growth and development. A continuous activation of proteins that are involved in important cell processes can lead to cancer, which is caused by an abnormal and uncontrolled division of cells.

Now that you hopefully understand some potentially fatal implications of the interactions of the Abl family of tyrosine kinases with other molecules, you may be wondering, how does one choose which proteins to explore in their interaction with Abl kinases? As my PI, Dr. Pendergast, explained to me, a former postdoc in the lab, along with the previous undergrad, who I mentioned earlier, conducted an unbiased screen for Abl2-induced tyrosine phosphorylated targets, which identified a specific set of kinases to be highly phosphorylated Abl targets. Moreover, it has been shown that these particular kinases are upregulated in breast cancer patients who develop resistance to diverse therapies. Thus, it is worthwhile to investigate and analyze the effects of the signaling axis between Abl kinases and these particular proteins.

Question: how many times can one say, “kinase” in a post? Read the above carefully to find out. 🙂

My research project has involved techniques that include culturing of various breast cancer and lung cancer cell lines, viral transductions, loss- and gain-of-function experiments, immunoprecipitations, and of course, western blots, the bread and butter of our research. I can’t wait to learn even more techniques and practice, practice, practice!

One of the core approaches my lab uses to model depressive-like symptoms in mouse models is the social defeat paradigm. This paradigm allows my lab to simulate behavioral conditions that lead to the onset of depressive-like symptoms which we can then use to study and/or treat. My lab uses this method because it allows us to study the onset of depressive-like symptoms in as close to a real world setting as possible, while not relying on the monoamine hypothesis that states that depression is largely caused by a lack of serotonin or norepinephrine in the brain. As the focus of my summer research work, I have been assisting various lab members on different projects that use the paradigm to study the effectiveness of different treatment methods for depression.

Currently, I am helping a fellow undergraduate student study the relationship between behavior and microbiology in the lateral habenula on the brain. Scientists have found that over excitability in the lateral habenula is correlated with depressive-like symptoms while a smaller region in the lateral habenula has been shown to inhibit these symptoms. Previous data has suggested that a protein, MeCP2, has an antidepressant like effect when phosphorylated in the small region of the lateral habenula. The project that I am assisting with seeks to understand whether MeCP2 is phosphorylated in the brains of mice that have been treated with an anti-depressant called imipramine.

The experimental set up involves 10 days of social defeat followed by 28 days of imipramine injections, or 27 days of saline injections and 1 day of imipramine injections. We will then test 6 mice out of each experimental group and 6 mice of the control group that receives 28 saline injections to isolate and measure MeCP2 levels in the lateral habenula. Our hypothesis is that the mice that have had 28 days of imipramine injections will have the strongest anti-depressant effects and will have the highest levels of MeCP2.

I had the pleasure of interviewing my post-doc, Dr. Stephen Mague, for this blog post. Dr. Mague attended Bates College for undergrad and got his PhD from the University of Pennsylvania.

I asked Dr. Mague why he chose to go into science. He said that he started off college taking science classes because he thought that he wanted to go to medical school. Though he originally saw his biology classes as a means to an end, during his junior year of college he discovered his love of neuroscience. It was a new, rare major that bridged his interests in psychology and biology so he began taking neuroscience classes. One such class was an animal models of behavioral disorders class where he got to do a class project and design an experiment studying Parkinson’s Disease in mouse models. He saw that it was possible to manipulate an animal’s behavior by changing brain levels of dopamine. Because of the class, Dr. Mague did a thesis project that extended his original work.

By the end of college, Dr. Mague was still in denial about being a scientist. He took three gap years working as a research technician where he learned more models of animal behavior, developed mouse surgical skills, and a love for studying animal behavior as it relates to neurological conditions. Dr. Mague was mostly motivated by intrigue in the general subject matter in which he was working and decided to go to grad school to pursue his interests.

Dr. Mague gave me some valuable insights that I would like to share with you all. First off, he explained that while grad school trains you to become a PI, most PhDs never become PIs. He said that it takes a specific skill set to be able to network, advocate for your lab, travel far and often, and be okay with being somewhat removed from the science that you work on. Next, he said that PhDs do not have to become professors either. He isn’t planning on ever teaching full time and has still made a career for himself in science. He said that there are many paths to go down in science besides the typical PI or professor route. Lastly, he said that it’s important to take care of yourself while you’re in school and not wait to live your life once you’re finished with school. I found this piece of advice to be particularly meaningful because I feel that at Duke it can be really easy to put yourself last behind all of your priorities. I think we can all learn a lot from what he had to say.

I really appreciate Dr. Mague speaking to me, and I found our conversation to be particularly informative and helpful. Though I couldn’t add all of our conversation to my post due to its length, all of what he said has helped me to focus on the importance of loving the science you do and realizing that the path you take may not be the path that everyone takes. It’s okay to make your own way in life and to be comfortable with yourself for doing so.

When presented with the opportunity to experience full-time research for the first time, expectations run wild. My excitement leads to visions of me in a lab coat conducting successful experiments every day and makes it difficult for me to ground my expectations in reality. Clearly no Nobel Prizes will be won this summer; I will not suddenly become the perfect scientist, and it’s unlikely that I’ll be running many experiments by myself. This summer is about learning, about growing, and about experiences that will mold my undergraduate career.

One of my more realistic expectations is to learn. After my first week in lab I truly believe that if I entered sleepwalking I would still manage to learn something. Learning in lab is different from learning in lecture in ways that you must experience. I didn’t learn where the mouse amygdala is by looking at a lecture slide; I saw the mouse amygdala! There’s nothing more exciting for me than getting to experience science by doing science and witnessing other talented people do science. My primary expectation this summer is that I will learn about neuroanatomy, the neuroscience of psychiatric disorders, and learn ways to properly use animal models to study models of human psychiatric disorders.

My scariest expectation is my expectation that I will grow (not literally) and change due to my participation in this summer program. For the first time, I get to try on my scientist hat and participate in real scientific questions and discoveries. I get to think of myself as a growing, learning researcher and discover all that that entails. I expect to grow in my knowledge of what it means to be a scientist. Do I like working in a lab? Do I like working with animal models? Do I fit in with my lab’s culture? Do I even genuinely like neuroscience or do I find more interest in a project conducted by one of my peers in this program? I hope to have answers to these questions by the end of the summer, and because of answering these questions I hope to grow.