January 18, 2019

Newly Recruited Faculty Bring Expertise in Key Research Areas

 
Translating Duke Health Logo

Thanks to a successful first year of Translating Duke Health (TDH), twelve new faces have popped up around the School of Medicine’s labs, clinics and meeting rooms. These new faculty members—representing a spectrum of career stages—were recruited to Duke because of their expertise in numerous fields including transplantation, neurosurgery, gene therapy, HIV, and more.  Known as Translating Duke Health Scholars, they will work with faculty across the School to advance research aimed at addressing major health challenges in five key areas: cardiovascular disease, children’s health, brain metastasis, brain resilience, and immunology. These hires represent the first wave of a large recruitment effort that will continue as the TDH initiative moves into its second year.

Meet the Translating Duke Health Scholars:

Priyamvada Acharya, PhDPriyamvada Acharya, PhD
Department of Surgery
Director, Division of Structural Biology, Duke Human Vaccine Institute 

This is an exciting time for HIV-1 vaccine research with multiple lines of approach showing promise for developing an effective HIV-1 vaccine. This is an exciting time for structural biology as well, with rapid and continuing progress in cryo-electron microscopy (cryo-EM) allowing unprecedented throughput and ability to determine structures of complex samples. Because my lab has expertise in both cryo-EM and x-ray crystallography, we are well-poised to take advantage of cutting edge structural techniques to further our research on HIV-1 entry and vaccine design.

The primary focus of my research is to understand how HIV enters cells in the body, and to use this basic knowledge for vaccines and therapeutics development. We use cryo-EM and x-ray crystallography to determine the structures involved in HIV-1 entry at atomic level resolutions. We are also interested in understanding the interactions of the HIV-1 Envelope (Env) protein with the human immune system. We do this by structural determination of complexes of HIV-1 Env with receptors and antibodies. Atomic level understanding of these interactions helps drive vaccine development. 

The Duke Human Vaccine Institute is a world leader in HIV-1 vaccine research. In addition to this, Duke has a strong structural biology community, emerging strengths in cryo-EM that include a state-of-the-art microscopy suite equipped with a Titan Krios microscope, and a supportive environment for new faculty. These were the major deciding factors for me in coming to Duke University.


Aravind Asokan, PhDAravind Asokan, PhD
Departments of Surgery, Molecular Genetics and Microbiology
Director of Gene Therapy, Division of Surgical Sciences, Surgery

This is an incredibly exciting time for gene therapy. Our lab focuses on understanding non-pathogenic viruses and tinkering with them so they can deliver therapeutics to different tissues in the body. We are particularly interested in applying these engineered viruses for gene therapy. The rationale behind gene therapy is that the root cause of many diseases is at the genetic level. No matter what modality you are looking at – whether it is gene replacement, gene editing, or gene silencing – essentially gene therapy is delivering the tools or the information that is going to correct that situation, in the form of DNA.  

There are already a couple of approved products with more on the horizon next year. We are on the verge of a whole new class of medicines. The exciting long-term research questions/breakthroughs are going to be: where else can we use this [gene therapy] approach beyond monogenic diseases? Can we use these viral tools successfully for genome editing?  In regenerative medicine, could we genetically manipulate tissues of interest and then use them for transplantation into patients? Are we going to be able to reprogram tissues to regenerate? 

We are tremendously excited to be exploring these new paradigms, and Duke is the place to do it. The spectrum of research opportunities, outstanding scientific community, and visionary administration at Duke can’t be beat.


Mihai Azoitei, PhDMihai Azoitei, PhD
Department of Medicine

After many years of research, the field of HIV vaccine design is at a point where promising pathways have been identified to develop an effective vaccine. Therefore, my work is focused on engineering immunogens that could become part of an HIV vaccine. 

I work on building proteins that will be effective as vaccines against HIV. Despite many efforts over the last 30 years, no vaccine exists that prevents HIV infection. I hope that the molecules developed in my lab and in collaboration with the other groups at the Duke Human Vaccine Institute, will “train” the immune system to fight and neutralize the virus in case of infection.

I came to Duke because of the excellent scientific environment that encourages collaborations and provides access to the resources necessary to do high impact research. My lab is part of the Duke Human Vaccine Institute, a world leader in vaccine research and development, where basic scientific discoveries can be rapidly advanced from the bench into the clinic.   


Francis Chan, PhDFrancis Chan, PhD
Department of Immunology

Cell death and inflammation are found in many human diseases. My passion is to understand how these two processes are connected with each other. Prior to joining Duke, my lab discovered a form of cell death called “necroptosis” that can powerfully stimulate inflammation.  I believe this knowledge is not only interesting at a basic level, but also has the potential to lead to better understanding of how we treat patients suffering from different forms of inflammatory diseases.

In the last few years, there have been numerous reports implicating necroptosis in inflammatory diseases from all tissue and organ origin.  These findings point to great promise for understanding how to treat these diseases better in the clinic.  However, effective therapeutic approach will require comprehensive understanding of the molecular mechanisms that regulate necroptosis.   This is the area where we hope to make the most impact and contribution.

There are strong interests from pharmaceutical companies to pursue necroptosis inhibitors as therapeutic agents for inflammatory diseases including inflammatory bowel diseases and rheumatoid arthritis.  The strength of clinical and translational research at Duke makes it an attractive place to merge our basic research program with more clinically-relevant investigation.


Sherika Hill, PhDSherika Hill, PhD
Department of Psychiatry and Behavioral Sciences

This is an exciting time to be studying biopsychosocial factors related to adolescent mental health and wellbeing because it is no longer cost prohibitive to conduct large-scale, whole-genome genetic and epigenetic studies. Also, there is a great amount of human genomic data available through free public databases.

Within this spectrum, I am cultivating a research agenda that seeks to understand the development of later psychopathology and chronic illnesses in adolescence based on exposures to early pediatric stress or trauma. In particular, I am curious how these adverse experiences correlate with epigenetic markers, such as DNA methylation and accelerated biological aging, which can disrupt normal biological processes and result in measurable clinical vitals including overweight/obesity and elevated blood pressure. In turn, these clinical indicators of poor or progressively worse outcomes over time substantially increase risk for chronic physical and mental health conditions. Examining these factors longitudinally and prospectively from birth is essential for both preventative strategies and timely clinical interventions.  

I chose to come to Duke because of its commitment to innovative, interdisciplinary, collaborative research to promote healthy childhoods by bridging clinical care, basic sciences, social sciences, informatics and policy.


Annette Jackson, PhDAnnette Jackson, PhD
Department of Surgery

The immune system has the ability to discriminate proteins as self versus non-self in order to protect the body from infection. Approximately one third of patients on transplantation waiting lists have generated antibody immune responses to non-self proteins as a result of exposure to blood transfusions, pregnancies, or previous transplants. These antibodies can prevent a patient from finding an acceptable donor or, if the patient is transplanted, these antibodies can significantly reduce the long-term survival of the transplanted organ. The Duke Transplant Center has identified a new treatment strategy that silences these antibody responses and holds the potential of creating safe and successful pathways to transplantation for many waitlisted patients. Leveraging my previous experience at Johns Hopkins, we will develop algorithms for monitoring the efficacy of this new treatment, aid in donor selection to avoid immune memory, and utilize new post-transplant immune monitoring tools to identify the earliest signs of rejection.

The Translating Duke Health initiative has recruited a prestigious group of transplant clinicians and researchers to the Duke Transplant Center with the goal of developing innovative strategies to improve transplant rates and longevity of transplanted organs. I wanted to be a part of this elite team to bring new molecular, serologic and bioinformatics tools into current medical practice and personalize immune monitoring strategies to reduce rejection incidence and improve long-term transplant survival. 

Leadership within Duke University School of Medicine has created opportunities to ignite cross-discipline research and facilitate the translation of basic science discovery into improvements in human health. In doing so, we are improving the quality of life for transplant recipients and creating a sense of hope and security for their families and loved ones.


Xunrong Luo, MD, PhDXunrong Luo, MD, PhD
Department of Medicine

It is an exciting time to be working in transplantation research. My primary research focus is to understand and find ways to control the body's immune responses against transplant organs, so that life-long immunosuppression in organ transplant recipients will no longer be necessary.  Ultimately, our research will identify the individual needs in controlling such immune responses, so that strategies to minimize and/or eliminate immunosuppression for each individual transplant recipient can be precisely predicted and optimally personalized. 

The past 50 years of clinical transplantation and related research have already built a strong foundation and a mature platform from which innovations can now sprout. Rapid advances in technologies have now made it possible for highly granulated histological, cellular and molecular details of transplant immunobiology to be obtained and archived at individual levels. Our capacity for computational analysis of large data banks is also rapidly advancing and is setting the perfect stage for processing high dimensional data sets and deriving complex algorithms for individualizing treatment options for transplant recipients.  Therefore, with necessary resources and seamless collaborations, we are entering an exciting new era of personalized transplantation. 

My decision to return to Duke is two-fold. First, I obtained both of my graduate and medical degrees from Duke in 1990s. Therefore, Duke is truly the institution that trained me to be the physician scientist I am today. With my past 20 years of experiences in transplant clinical and basic research, I feel that the timing is now mature for me to return to Duke to contribute my knowledge and expertise to advancing the academic mission of Duke. Secondly, Duke has the nation’s leading experts in transplant surgery, nephrology, pathology and immunology, all of which form the basis of the collaborative network for my research.  Integrating into such a collaborative network with its collectively expertise, we are perfectly positioned to accelerate scientific discoveries in transplantation and to translate scientific innovations into transplant clinical practice. 


Ashley Moseman, PhDAshley Moseman, PhD
Department of Immunology

We are hoping to learn how olfactory barrier defense juggles its requirement to protect the brain, yet also smells efficiently. In addition, we are interested in further understanding how the brain and hematopoietic system are able to sometimes work cooperatively to drive infections from the brain, and yet other times, they fail. My goal is to understand the mechanisms that pathogens use to breach the olfactory barrier; how immune cells work in concert with the parenchymal cells of the olfactory epithelium to form a barrier; and how this barrier can be compromised. Once the olfactory barrier has been compromised, pathogens can access the central nervous system (CNS). 
 
The School of Medicine has invested in a state-of-the art intravital multiphoton microscope that will allow us to visualize cellular interactions within the CNS of living animals. In particular, this microscope will allow our group to better understand the host-pathogen interactions that drive central nervous system diseases, like PAM. Our hope is that insights from understanding basic anatomical mechanisms of olfactory to CNS communication and barrier function will have implications for a number of human diseases including infectious diseases, neurodegeneration, as well as cancer therapies.
 
Single cell RNA sequencing technology is providing us the ability to gather enormous amounts of information on cell populations we would not have been able to decipher without years of guesswork and labor. These data sets generate nearly limitless genomic foundations for hypothesis driven research. In addition, systems biology and the ability to render massive data sets into workable data sets is transforming basic research. At Duke in particular, there is a great deal of support for cross-disciplinary collaboration which fosters opportunities for different specialists to come up with ideas they’d not typically even considered.
 
Duke obviously has a reputation for excellence. One of the big attractions was the relatively centralized nature of the medical research facilities. At some institutions the hospital and clinical departments are quite physically separated from graduate and undergraduate campuses. But the tight proximity of things at Duke was appealing because it’s obviously easier to find and interact with collaborators when you are nearby. The youthful vigor that you find at Duke and Durham have been exactly what we were looking for.


John Pearson, PhDJohn Pearson, PhD
Department of Biostatistics and Bioinformatics

I'm interested in data. More specifically, I'm interested in what data can tell us about how the brain functions, and how new ways of looking at that data can give rise to new theories and suggest new experiments. My lab works on new analysis methods for neuroscience data, from the dynamics of social interaction to vision in the retina.

The amount of data collected by neuroscience researchers is growing exponentially. Machine learning is constantly in the news, and much of the hype is justified. The BRAIN Initiative began under President Obama in 2013 with the ambitious goal of recording the activity of every cell in the brain, but the real challenge is what to do with that information when we have it. My goal is to provide mathematical and computational tools that help experimenters better test new ideas, whether that be analyzing data in real time or understanding rich and complex behaviors.

I came to Duke for my postdoctoral training. I decided to stay at Duke both because my family loves Durham and because Duke provides a real home for the kind of interdisciplinary research my lab does. I'm in a quantitative department in the medical school, but my lab is located directly between the cognitive neuroscientists and the neurobiologists. That wouldn't be possible many other places.


Derek Southwell, MD, PhDDerek Southwell, MD, PhD
Department of Neurosurgery

I am interested in understanding how brain cells (neurons) develop during early life, and how their dysfunction results in disease conditions. I am also studying the transplantation of neurons as a prospective treatment for nervous system disease and injury.
 
Advances in imaging, device manufacturing and informatics have allowed neuroscientists to measure and characterize brain function in numerous dimensions.  We can now observe the brain's microscopic cellular components in action, both individually and in large aggregates of thousands or millions of cells.  We are beginning to grasp how patterns of cellular activity represent what we see and hear, and how they give rise to our movements, speech and moods.  This knowledge has potential to drastically improve medical care for patients with neurologic disorders and injuries.  As a physician with a strong interest in neuroscience, my intention is to see that the promise of this research is realized for patients.   
 
It takes significant resources and inspiration to pursue translational research.   Through TDH, Duke is directing its strengths in science and engineering towards the development of transformative clinical therapies.  One of my professional goals is to advance patient care through translational neuroscience, and Duke is one of the few universities that can really support this type of work.


Neil Surana, MD, PhDNeil Surana, MD, PhD
Departments of Pediatrics, Molecular Genetics and Microbiology

Work over the past 15 years has demonstrated a clear association between the human microbiota—the trillions of bacteria, viruses, fungi, and Archaea that live in and on each of us and outnumber human cells by at least 10-fold—  and a variety of different disease states, ranging from inflammatory bowel disease to Parkinson’s disease to cancer. The field of microbiome research has made great strides in cataloguing the “normal” microbiota, and it now stands at the precipice of an ability to treat the fundamental basis of many diseases. Given its putative central role in driving disease pathogenesis, the microbiota is considered to represent an untapped treasure-trove of therapeutics.

My research seeks to understand how the microbiota influences susceptibility to inflammatory disease. More specifically, I seek to identify and characterize “healthy” bacteria that can modulate the immune system, with the ultimate goal of translating these bacteria and/or their products into clinical practice to treat various inflammatory and autoimmune conditions.

Duke is widely known as a clinical powerhouse, and it also has burgeoning strength in microbiome-related research that is supported by the recent advent of the Duke Microbiome Center. Given my interest to work on translational aspects of the microbiome, the decision to come to Duke was an easy one. My hope is that I will be able to help cross-pollinate ideas between the clinical and basic science worlds to ultimately accelerate the development of microbiota-based therapeutics.


Andrew West, PhD
Department of Pharmacology and Cancer Biology

The last 20 years of research has pinpointed the critical action of just a few proteins in the most common neurodegenerative diseases, and tools are just becoming available to test whether these proteins are as important as we think they are in the progression of disease. Many of us are optimistic that soon Parkinson’s disease and Alzheimer’s disease will become problems of the past.

Our lab focuses on mechanisms underlying neurodegenerative diseases and experimental therapeutics that might slow or halt disease progression. I chose to come to Duke because it offers substantive research infrastructure and a multidisciplinary collaborative environment.

 

Friday, January 18, 2019