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Celebrating Research: 2016 Young Investigators’ Day Winners
From uncovering the retina’s own circadian rhythm to revealing the humanlike pitch perception in ancient monkeys, discoveries by our trainees have helped propel research endeavors at Johns Hopkins Medicine.
The annual Young Investigators’ Day ceremony celebrated the unique contributions of 20 junior researchers, and the mentors who helped them get there.
Meet this year’s awardees and learn more about their extraordinary work, both in and outside the lab.
Amit Agarwal: W. Barry Wood Jr. Award
Mentor: Dwight Bergles
Project Details: Maintaining connections between the neuron and glia cells in the brain are essential for its precise functioning. However, the mechanisms by which neurons and glia communicate to assemble a conscious brain are not well understood. To study one of most numerous glial cell type called astrocytes, I developed novel mouse genetics tools and combined advanced microscopic techniques and computational methodologies. Using these tools and technologies, I uncovered a novel mechanism by which norepinephrine, a neurotransmitter released by neurons when we are trying to be attentive, stimulates astrocytes to enhance energy production to support anticipated neuronal activity. This finding reveals a new mechanism by which brain actively regulates its energy demands. Any disturbances in such delicate cross-talk between neuron-glia can lead to improper support of neurons by glia, which can contribute to various neurological and psychiatric disorders. Learn more about Amit's work and the Dwight Bergles Laboratory.
What’s Next: Currently, I am looking for a faculty position. I want to set up my own laboratory and explore the various role of enigmatic glial cells in the brain.
Kate Chiappinelli: A McGehee Harvey Award
Mentor: Stephen Baylin
Project Details:My work has shown that cancer drugs that remove the DNA methylation "tag" that prevents genes from being expressed can boost anti-viral immune signaling from tumors. I and my colleagues showed that this was due to the DNA methylation inhibitors activating viral RNA that is normally silenced in our genomes. We hope that this treatment can improve the effects of immune therapy in patients with cancer. Learn more about Kate's work.
What’s Next: I am currently interviewing for assistant professor positions.
Trevor Davis: Paul Ehrlich Award #4
Mentor: Stephen Yang
Project Details: My work has been focused on perioperative factors associated with readmissions after lung cancer surgery. We found two factors associated with increased odds of 30-day readmission: having a postoperative complication and being discharged from surgical stay with an unresolved complication. These results will help to guide further research, lay a strong foundation for nationwide readmission prevention and allow for the development of a risk stratification tool to better detect susceptible patients.
What’s Next: I have just finished my preclinical years of medical school and am looking forward to starting clinical rotations in the hospital.
David Herzfeld: Martin and Carol Macht Award
Mentor: Reza Shadmehr
Project Details: We know that the cerebellum, the oldest part of the brain, is important for accurate movement of the eyes, and damage to this region results in inaccurate movements. This suggests that the discharge of cells in the cerebellum (Purkinje cells) should be related to eye movements. However, previous results have not been able to establish the relationship between neuron firing rates and eye movement parameters.
To answer this question, we examined how a population of Purkinje cells changes its activity in concert, rather than focusing on an individual cell. Our findings suggest the cerebellum is integral for the control of eye movements and, when examining a large population of cells in the cerebellum, these cells provide a representation of the speed and direction of the eye. Learn more about the Laboratory for Computational Motor Control.
What’s Next: I am preparing to graduate this year, but I anticipate continuing to work in our laboratory as a post-doctoral fellow for the immediate future.
Maximilian Konig: Albert Lehninger Award
Project Details: In patients with rheumatoid arthritis (RA), an abnormal immune response is directed against citrullinated self-proteins, leading to inflammation and joint destruction. We investigated the link between periodontal disease, a bacterial-induced inflammatory disease of the gums, and RA to identify microbial species that may trigger citrullination and have potential to initiate autoimmunity. By studying patients with gum disease, we identified a unique oral pathogen that drives protein citrullination in the periodontal pocket by activating immune cells. We also found that infection with this pathogen is prevalent in patients with RA and associated with the appearance of rheumatoid factor and disease-specific antibodies against citrullinated proteins (ACPAs).
These findings open the possibility to identify populations at risk and to explore novel treatment approaches beyond immunosuppression in this chronic and still incurable disease.Learn more about the Felipe Andrade Lab.
What’s Next: I am currently finishing my postdoctoral fellowship to continue clinical training. I will be joining the internal medicine residency program at Massachusetts General Hospital in Boston. My long-term goal is to work as a physician-scientist in rheumatology and continue to explore fundamental mechanisms that may initiate autoimmunity in these diseases.
Bram Lambrus: Alicia Showalter Reynolds Award
Mentors: Andrew Holland
Project Details: Mitosis is a high-risk period of the cell cycle, requiring stringent quality controls to ensure that daughter cells receive the appropriate DNA content for future growth and development. Centrosomes are organelles that form the poles of dividing cells. These organelles have been difficult to study due to a lack of methods to manipulate them. We generated a chemical genetic tool to inducibly deplete centrosomes, and discovered a protective surveillance pathway that prevents cells from entering the cell cycle when they lose centrosomes. We then performed a genome-wide knockout screen that identified several components of this novel pathway, helping us understand how cells recognize and avoid dividing in conditions that could lead to genomic instability. Learn more about the Holland Lab.
What’s Next: I look forward to exploring the mechanism of this novel surveillance pathway in the next few years of my graduate career.
Jieun Lee: David I. Macht Award
Mentor: Michael Wolfgang
Project Details: My research focuses on whether the use of fats for energy is required for various processes throughout the body. We have shown that the use of fats for energy in tissues, such as the adipose, liver and brain, is critical to maintain energy homeostasis. I was especially interested in the adipose tissue because it has been suggested that increased fatty acid oxidation in brown adipose tissue can alter body weight, potentially being a way to treat obesity and diabetes. So far, we have shown that fatty acid oxidation in adipose tissue is required to maintain body temperature, but it does not play a role in altering body weight or insulin resistance. Learn more about Jieun' s work and the Michael Wolfgang Lab.
What’s Next: I will be graduating in September and continuing as a postdoc at Johns Hopkins while applying for medical school. I would really like to go to medical school to continue my research career as a clinician.
Jonathan Ling: Mette Strand Award
Mentor: Philip Wong
Project Details: TDP-43 is a protein implicated in several human diseases including amyotrophic lateral sclerosis (ALS, or Lou Gehrig’s disease) and frontotemporal dementia, but its normal role in cells remains unclear. We found that, in healthy cells, TDP-43 helps to prepare viable strands of mRNA by preventing the inclusion of sequences that would otherwise cause the mRNA to be destroyed and never translated into protein. When TDP-43 clumps together in diseased cells, it can’t do its job and lots of protein go unmade. With luck, our discovery may lead to new therapeutic strategies for ALS or frontotemporal dementia. We have also begun to expand upon this discovery to identify proteins with similar roles, which may have important implications for understanding certain types of mutations in human disease. Learn more about Jonathan's work and the Philip Wong Lab.
What’s Next: I plan to finish my Ph.D. within the year and am currently looking for a postdoctoral position.
Sha Liu: Alfred Blalock Award
Mentor: Mark Wu
Project Details: It used to be thought that the naturally increasing desire to sleep was governed by the buildup of small molecules signaling to cells in the brain. In my research, we demonstrated that this “sleep pressure” actually comes from changes in the activity of newly identified brain cells. This new view on sleep biology provides an explanation for the gradual buildup and persistence of sleep pressure, as well as a new conceptual framework for future investigations into the regulation of sleep. Learn more about Sha's work.
What’s Next: I will look for faculty positions next year.
Alisa Mo: Michael A. Shanoff 1 Award
Mentor: Jeremy Nathans
Project Details: Ideveloped a new method to capture nuclei from targeted cell types and combined it with genome-sequencing techniques to explore global variations in gene expression, DNA methylation and regulatory networks across brain neurons. This work gives insight into neuronal diversity in the brain and could provide valuable insight into neuropsychiatric disorders. Learn more about Alisa's work and the Jeremy Nathan Lab.
What’s Next: Currently, I am a third year medical student, and in the fall, I will be applying for residency programs.
Mike Morgan: Daniel Nathans Award
Mentor: Cynthia Wolberger
Project Details: Most genes are kept inactive by being coiled around balls of proteins to form nucleosomes. Uncoiling a segment of DNA often begins with the action of a chromatin eraser enzyme to remove a small protein tag, called ubiquitin, from a nucleosome. We figured out the first molecular structure of a chromatin eraser enzyme, known as the DUB module, which is part of the SAGA complex. Essentially, we got a really detailed look at how the DUB module attaches to a nucleosome before it removes a ubiquitin. Since the human DUB module is overabundant in cancers for which no good treatment options exist, we hope that our work will lead to new drugs that target the interaction of the DUB module and the nucleosome.
What’s Next: Over the next year, I intend continue my work in the Wolberger lab and pursuing other exciting projects pertaining to the human homologue of the SAGA deubiquitinating module involving cutting-edge biophysical techniques, such as single-molecule fluorescence and cryo-EM.
Siew Cheng Phua: Hans J. Prochaska Award
Mentor: Takanari Inoue
Project Details: Primary cilia are tiny hair-like structures on cell surface that serves as an antenna sensing ever-changing environmental conditions. Genetic studies have associated primary cilia with diseases such as polycystic kidney disease and cancer. However, the tiny dimensions of primary cilia have made it difficult to study them using traditional cell biology techniques to figure out how they work. To address this, members of the Inoue lab and I have developed molecular “spies” that allow us to precisely control the activities of proteins and watch them move around. They discovered new roles for calcium and the molecule phosphatidylinositol 4,5-bisphosphate, which help regulate the chemical and mechanical function of cilia. This information helps researchers to understand how diseases develop when primary cilia become mutated. Learn more about Siew's work and the Inoue Lab.
What’s Next: I will be graduating later this year and will return to Singapore for postdoctoral fellowship.
Yun Qing: Paul Erlich Award #2
Mentor: Duojia Pan
Project Details: The Hippo pathway is an emerging pathway in organ size control and tumorigenesis. My research discovered the recruitment of the histone H3K4 methyltransferase complex to the core transcriptional coactivator Yki. The specific histone modifier could be a novel target for anticancer therapy. Learn more about Yun's work and the Duojia Pan Lab.
What’s Next: I plan to graduate this year and am wrapping up my current projects.
Xindong Song: Bae Gyo Jung Award
Mentor: Xiaoqin Wang
Project Details: For a long time, researchers thought humans perceived pitch from sounds using different mechanisms than other mammals. My study showed behavioral evidence that marmoset monkeys also exhibited all the primary features of human pitch perception mechanisms. The study also paves the way for future research into the neuronal circuitry underlying human-like pitch perception. Learn more about Xindong's work and the Xiaoqin Wang Lab.
What’s Next: I'm continuing to work in the same lab, trying to dissect the underlying neuronal circuitry of human-like pitch perception mechanisms in marmosets. I'm developing more sophisticated tools like noise-free two photon microscopy, minimally invasive optogenetics and trying to apply them in monkeys.
Han Chin Wang: Paul Erlich Award #1
Mentor: Dwight Bergles
Project Details: My study investigated the mechanism of spontaneous electrical activity during the development of the nervous system before any inputs from external environment are available. Although this activity presents in different regions of the brain and across different species, we still don’t fully understand how this activity influences the maturation of neural circuits. Using rodents as animal models, my thesis work identified the molecular pathway involved in generating spontaneous activity in the developing auditory system. We also identified a particular molecule, calcium-activated chloride channel TMEM16A, as the key component in this process. By removing TMEM16A from the mouse cochlea, we have generated a genetic animal model that exhibits much less spontaneous activity, which can be used for studying the functional roles of spontaneous activity in the developing auditory circuits. Learn more about Han's work and the Dwight Bergles Lab.
What’s Next: I am currently doing postdoctoral research at the University of California, Berkeley.
Hongdian Yang: Paul Erlich Award #3
Mentor: Daniel O’Connor
Project Details: I study the neural circuit mechanism for touch perception. My postdoc work revealed the progression of neuronal activity that predicts perceptual choice across neural circuits in a mouse’s somatosensory system. Learn more about Hongdian's work and the O'Connor Lab.
What’s Next: I want to start my own lab and am currently looking for junior faculty positions.
Wendy Yue: Michael A. Shanoff 2 Award
Mentor: King-Wai Yau
Project Details: One of my projects was to study how the retina, the only tissue known to ignore the body’s circadian rhythm, keeps itself on schedule. Our team found that the retina uses neuropsin, a protein found in nerve cells and responds best to UV-A, to keep itself synchronized with the external light-dark cycles. Learn more about Wendy's work and the King-Wai Yau Lab.
What’s Next: I shall stay as a postdoc in King’s lab to finish some work and then move onto a postdoc position in another lab.
Ke Zhang: Helen B. Taussig Award
Project Details: My research sheds light on the nucleocytoplasmic transport cellular pathway as a key mechanism in the pathogenesis of two devastating neurodegenerative diseases: amyotrophic lateral sclerosis (ALS) and frontotemporal dementia. Our research suggests that targeting this pathway may be a potential therapeutic strategy. Learn more about Ke's work.
What’s Next: I am extending my studies in the ALS field in the same lab at Johns Hopkins. I plan to lead my own independent research group after being prepared.