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ASGCT

New Investigator of the Month

Who are the faces of ASGCT?

ASGCT's New Investigator of the Month profiles an ASGCT member who is new to the field or just beginning an independent position. To be considered for a future New Investigator of the Month, applicants must be an Active or Associate Member of the Society. Active Members must be 10 or fewer years out from their first active, independent position.

Please click here to apply or nominate a colleague. New Investigators of the Month are selected by the ASGCT New Investigator Committee.


Paloma H. Giangrande


Questionnaire

Briefly describe how your reached your current position

I obtained my PhD at Duke University in 1999 when the therapeutic potential of RNAi-based therapies had just been unveiled. This moved me to pursue postdoctoral training positions in Academia and learn about breakthroughs in cell/molecular biology and RNA therapeutics. My first postdoc position was under the mentorship of Dr. Joseph Nevins in the Department of Genetics at Duke. It was in Joe's lab that I demonstrated that distinct E2F isoforms (E2F1, E2F2, and E2F3) regulate different subsets of genes. Given the impact of these findings at the time, this work resulted in several publications in high-profile, peer-reviewed journals. In 2004, I became interested in translational research and was ecstatic to have the opportunity to work in the lab of Dr. Bruce Sullenger in the Department of Surgery at Duke University.  For the next 3 years I focused on developing RNA aptamers for targeted therapies. The work in Bruce's lab resulted in high-profile publications that enabled me to apply for faculty positions in Academia. In 2007 I was appointed Assistant Professor in the Department of Internal Medicine at the University of Iowa. Last year I was promoted to Associate Professor and remain excited about the promise of oligonucleotide therapies for treating disease.

What do you view as your greatest scientific achievement to date?

Perhaps, my most significant contribution to the field to date has been the discovery of a novel avenue for targeted delivery of siRNAs. In response to the need for robust delivery techniques that allow the application of these therapeutics to increasingly complex disease and organ systems, my lab has pioneered a simple, all-RNA approach that utilizes RNA aptamers to target and deliver siRNAs to specific cell types in vivo. Our approach selectively targets the siRNA to the cell-type of interest, thereby reducing unintended effects that can result from non-specific delivery as well as reducing the amount and cost of siRNA needed for therapeutic purposes. In our initial study, we showed that RNA aptamers can deliver siRNAs targeting cell-survival genes to prostate cancer cells expressing prostate specific membrane antigen (PSMA) in vitro and in vivo. Based on the simplicity and potential clinical impact of our approach, our original paper describing the use of aptamer  s for targeted delivery of siRNAs has been cited over 400 times since 2006 (Google Scholar). We soon recognized that for future clinical development these reagents must be effective when administered systemically and must be amenable to efficient chemical synthesis. We thus sought to improve the delivery and activity of our first-generation RNA aptamer-siRNA chimera directed against prostate cancer. Whereas the earlier chimera required intratumoral injection for efficacy, the second generation chimeras were optimized to achieve in vivo efficacy after systemic administration. This was the first description of in vivo efficacy of a systemically administrated aptamer-siRNA chimera and thus represents a milestone for this platform technology. Given the impact, this work was featured in a News & Views article in Nature Biotechnology and has been cited over 130 times since 2009 (Google Scholar). An important aspect of the aptamer-siRNA chimera technology is its general applicability. Sinc  e our initial study, aptamer-siRNA chimera-based therapeutic approaches have been developed for prostate cancer and HIV. The availability of cell-internalizing aptamers specific for the prostate cancer antigen, PSMA, the HIV glycoprotein, gp120, and the CD4 receptor expressed on T cells, has enabled the evaluation of RNA aptamers as delivery vehicles for siRNAs and, importantly, the establishment of design rules for optimal processing of the aptamer-siRNA conjugates by the RNAi machinery. To date, multiple studies, by several groups, have reported efficacy of systemic administration of aptamer-siRNA chimeras in mice with doses under 1mg/kg. These advances highlight the potential for translating this technology in humans.

In what ways do you feel the ASGCT has played a role in your scientific and career development?

ASGCT has been a true portal to the field of gene and cell therapy. Over the years, it has exposed me to many of the leaders in the field and has enabled me to mentor young scientists in other institutions around the country. The commitment of the ASGCT to the field inspires me on a daily basis to do what I do.

Where do you see yourself 10 years from now?

I hope to be lucky enough to be doing what I am doing now. Mentoring the next generation of scientists and working to enhance our understanding of human diseases and to develop safer, more effective therapies to treat these diseases. I would not change anything...

In light of your accomplishments, what advice would you offer to your ASGCT colleagues with respect to research and/or career development?

"Just Keep Swimming" Dory (Finding Nemo) ...and never give up on your passion and dreams!

How do you like to pass the time outside of work?

I love to spend time with my 3 year old and play dress-up. When I have to act like an adult I enjoy reading, running and cooking.



Gary J. Brenner


Questionnaire

Briefly describe your research interests

My laboratory currently focuses efforts on the development of novel therapeutic strategies for the treatment of Schwann-cell derived nerve sheath tumors.  In particular, we are utilizing adenovirus associated vectors to deliver caspase-1 to tumor cells.  Delivery of this apoptosis-generating transgene both directly kills tumor cells in which it is expressed and activates anti-tumor host responses.  We are investigating the mechanisms through which our vector kills tumor and are developing the therapeutic strategy for translation into phase 0/1 clinical trials

Briefly describe how you reached your current position (educational background)

A significant component of my PhD work which was in Microbiology and Immunology focusing on neuro-immune interactions, involved use of a pulmonary tumor model in mice to investigate neuro-endocrine influences on metastasis.  During post-doctoral training, my focus moved to the neurobiology of pain.  This work involved animal modeling of pain which required significant expertise in animal surgery and behavioral testing of sensory function.  More recently, I have developed a focus on modeling and development of novel treatment strategies for neurofibromatosis.  Interest in this area was largely motivated by my clinical work (which is entirely in pain medicine) with patients with nerve sheath tumors.  These individuals frequently present with severe pain that for which there is often no efficacious treatment.  Thus, my scientific and clinical training provides the skills necessary to implement the proposed animal studies, as well as, continue to work on the project should results allow translation to clinical trials.

What do you view as your greatest scientific achievement to date?

The scientific achievement of which I'm most proud relates to the efforts to develop a gene therapy for the treatment of the neurofibromatoses.  The work to date has led to a successful 5-year R01 award, a few publication including that in Human Gene Therapy publication (2013;24(2)152-62), and a recent patent application titled "Gene Therapy Induced Pyroptosis for the Treatment of Tumors."  It would be entirely inappropriate for me to list these achievements without mentioning a few of my collaborators without whom these successes would not have been possible - Xandra Breakefield, Miguel Sena-Esteves and Giulia Fulci.

What, in your opinion, marks the greatest advance to date in the field of gene and cell therapy and why?

First, the 2012 acceptance by the European Commission of Glybera (for the tx of lipoprotein lipase deficiency) marks a major milestone for the gene therapy community.  Second, the development and clinical testing (there multiple ongoing Phase III trials) of oncolytic viruses hold the real potential of applying gene therapy strategies to a variety of malignancie

In what ways do you feel the ASGCT has played a role in your scientific and career development?

 ASGCT has provided an exceptional environment for interaction with investigators from a broad spectrum of fields.  This has been especially helpful for me - an investigator relatively new to the field of gene therapy.



Adrian Timmers, PhD


Questionnaire

Briefly describe your research interests

As a graduate student I studied retinal pigment epithelial (RPE) cells. The RPE cells form a single layer of epithelial cells positioned between photoreceptor cells and a basement membrane (Bruchs Membrane).  The importance of RPE cells in sustaining retinal functioning and survival has captured my interest for a long time.  RPE cells are vital for visual pigment regeneration (Vitamin A metabolism), they form a gateway for nutrient flow to photoreceptor cells and are the processors of spent photoreceptor outer segment tips. RPE cell dysfunction can result in vision impairments with major economic consequences and quality of life issues for instance age-related macular degeneration.  The understanding of the interaction of RPE and photoreceptor cell, the pathology associated with this interaction and search for a therapeutic approach drives my research.  Toward these goals, the methods of delivery of therapeutic genes to ocular tissue with virus, nano particles or other methods, embody the most important aspects of my research interest.

Briefly describe how you reached your current position

As a graduate student I took a position in the department of Biochemistry at the University of Nijmegen, The Netherlands.  My project targeted the big question of the day: where does the 11-cis isomerization of retinoids take place? Is it in the photoreceptor or the RPE cell? I developed a whole eye perfusion method to isolate intact RPE cells from fresh bovine eyes. The RPE cells were incubated with radiolabeled all-trans retinol and the metabolites were analyzed by HPLC. My results confirmed Bernstein and Rando’s data that indeed it’s in the RPE cells where the isomerization takes place. Retinol is the substrate for isomerization followed by an immediate esterification to fatty acids.  Upon completion of my doctorate, I took a post-doctoral position in the labs of Paul A. Hargrave and William W. Hauswirth at the University of Florida to further my education in retinal development and molecular biology of vision.  At the U of F, I developed a simple and robust method for subretinal injections in rodent eyes, a tool that became important for the research on gene delivery to photoreceptor cells and RPE cells.  Following my tenure at the U of F, I took a position in the research labs at Alcon, the leading pharmaceutical company in eye care. At Alcon I worked on the development of treatments for diabetic retinopathy and viral infections.  Furthermore my team applied siRNA to treat eye diseases. Currently, I reside in the greater Boston area and am exploring the opportunities in the local pharmaceutical and biotechnology industry

When and why did you first develop an interest in gene and cell therapies?

Initially my focus was on embryonic retinal development in bovine eyes. Later my focus switched to understand the molecular biology of retinal degeneration and to develop novel therapies. To date, approximately 250 loci have been mapped for retinal degenerations of which approximately 200 genes have been identified (https://sph.uth.edu/retnet/).  Scientific curiosity combined with the emotional and economic impact of loss of vision led to my decision to search for ways to change the course and outcome of retinal degeneration.  The conceptual simplicity and elegance of gene therapy was appealing hence I joined the AAV effort at the University of Florida. The progress made in the field of gene therapy since the end of the last century is astounding and one day it will be a standard part of clinical practice in many disease areas.

In your opinion, what are the greatest areas of need which must be addressed to ensure continued progress in this field?

Efficient delivery to and uptake of the transgene (therapeutic or investigative) by the target cells has been an enormous challenge, most prominently so for non-viral mediated gene delivery.  Viruses have evolved to transfer genetic material with high efficiency to their natural target cells. However, successful gene therapy requires the ability to modify existing tropism to deliver the genetic payload to cells of interest.  An illustrative example is given by Dalkara and coworkers (Dalkara et al., 2013 Sci Transl Med, 5: 189ra76).  Through directed evolution, an AAV variant was isolated that displayed a modified delivery profile to retinal tissue.  Furthermore, the field of gene therapy depends on progress with regard to the regulation of transgene expression (induction and duration of transgene expression).  In addition, the option to activate a ‘kill signal’ to permanently shut down transgene expression will be an important safety feature needed to ease potential unintended long term side effects.  Lastly, continuous progress depends on tackling neutralizing immune responses against viral delivery vehicles.  Such immune responses could present formidable hurdles for repeat applications of viral gene therapy.

How do you like to pass the time outside of work?

I love to go on long walks with my wife and our dog and I love my challenging, enduring bike rides.  Both of these activities help me to clear my mind and reset my focus on today and strengthen a general sense of gratitude. 



Takeshi Suda, MD


Questionnaire

Briefly describe your research interests

 I currently focus my research on the development of a hydrodynamic gene delivery system which suits clinical use by coupling a computer-controlled injection device and interventional radiology.

In particular, my goal is to establish a way to impart survival advantage for impaired hepatocytes by in vivo delivery of a vector, which segregates in an episomal fashion.

When and why did you first develop an interest in gene and cell therapies?

My first involvement in research came in a mouse genome project under the tutelage of Professor Ryo Kominami, then shifted to investigate telomere length regulation in gastrointestinal disorders, especially liver diseases. Chronic liver diseases pass the same road to liver cirrhosis/hepatocellular carcinoma irrespective of their etiologies. As a hepatologist, I have witnessed numerous horrific diseases, for which only supportive care is available even though there is sufficient time to eradicate the affected cells and reestablish a healthy liver before senescence takes place. Such experiences have inspired me to believe that a long-term cure is achievable if we can produce genetically healthy self-hepatocytes in the liver.

Because I have been made to realize the toughness and viciousness of viruses through the unfortunate cases triggered by viral infection, I decided to open a door to learn the fundamentals of the most efficient nonviral gene delivery vector.

What do you view as your greatest scientific achievement to date?

It has been my privilege to work with Professor Dexi Liu and his colleagues initially at the University of Pittsburgh and thereafter at the University of Georgia in searching for a key determinant for efficient hydrodynamic gene delivery and implementing the results into a gene delivery system feasible for large animals.

In your opinion, what are the greatest areas of need which must be addressed to ensure continued progress in this field?

For both gene therapy and cell therapy, the integration into genome is one of the most serious concerns in this field as long as genetic materials were transferred for cell modification. Current knowledge and technologies in medicine are sufficiently developed to take care of acute physical disturbance, while the integration give rise to latent risk due to reactivation of imprinted genes or other genetic imbalance. I believe that the technological development of a convenient way to deliver genetic materials segregating in episomal fashion is the greatest area of need.

Furthermore, gene and cell therapy should be realized in an entire framework of patient care including conventional remedies. Modified parenchymal cells can attain patient wellbeing only under a suitable tissue environment and niche. A mutual connection between ASGCT and the medical society would be the greatest avenue to establish a next generation of patient care.

In light of your accomplishments, what advice would you offer to your ASGCT colleagues with respect to research and/or career development?

My mentor in clinic taught me that a good physician is required to have both an angel’s sensitivity and a devil’s durability. I think it is also true for a good researcher.

How do you like to pass the time outside of work?

Physical starving and exhaustion make people sensitive to feel what happens in your body; shifting metabolic sources from sugar to fat, accumulation of lactate, edema mobilizing cells for tissue reorganization, and so on. My wife and I love running marathons, camping and other outdoor activities. When attending a conference in an unfamiliar place, I enjoy running through the city to get a true feel for it.



David Markusic, PhD


Questionnaire

Briefly describe your research interests

Developing therapies to reverse pre-exisitng immunity against clotting factors in hemophilia and extending these therapies to treat autoimmune disease

Briefly describe how you reached your current position (education background)

I obtained my BS from UCSD in a Bioengineering Premedical program with more of an emphasis on biology.  I received a MS in Molecular Biology from the University of Amsterdam with two research internships in yeast mitochondrial protein assembly and defining the role Egr1 protein in oncogenesis.  I obtained my PhD also from the University of Amsterdam at the Academic Medical Center, Division of Experimental Hepatology focussing on developing lentiviral vector platforms for regulated liver directed gene transfer.  My postdoctoral training was in the laboratory of Roland Herzog where I focused on testing immunological responses against novel AAV vector serotypes for hemophilia B gene transfer and the role of liver gene transfer in reversing on-going immune responses.

When and why did you first develop an interest in gene and cell therapies?

Since I can remember my first exposure to science in school I have always had an interest in biology and chemistry.  My senior year in high school we were tasked with doing a career report and I chose gene therapy as my focus.  So this was back in 1990 and I was able to interview a researcher in academia and industry and was pretty excited about their thoughts about gene therapy and molecular biology and where the field may be heading.

What do you view as your greatest scientific achievement to date?

I would have to say that the work we recently published regarding the protective role of AAV8 hF9 liver gene transfer in reversing ongoing immune responses against recombinant human factor IX protein.  Not only did this therapy provide protection against fatal anaphylactic responses and prevent the generation of new anti-hFIX antibodies but it also provided long-term corrective factor IX protein expression.  I think that this study addressed an important issue in evaluating the safety and efficacy of gene transfer in hemophilia B, in which the patient may develop antibody responses to the therapeutic protein. Liver gene transfer may offer a new or complementary approach to immune tolerance induction protocols in hemophilia and in other inherited disorders that require enzyme replacement therapy.  Additionally this approach may be translated into a new therapeutic approach to treat autoimmune diseases.

What, in your opinion, marks the greatest advance to date in the field of gene and cell therapy and why?

This is a difficult question to answer without probably upsetting the many individuals who have made important historical contributions to the field.  I will also admit to some bias since I have been working with AAV vectors for so long that I can best narrow this down to the recent success of clinical trials for leber's congenital amaurosis and hemophilia B.  I certainly would be remiss not to mention the landmark success of other clinical trials such as for SCID and ADA immune deficiencies involving retroviral gene transfer to HSC.  But I see the positive outcomes with LCA and hemophilia B trials as a kind of fulfillment of a promise that we as scientists and clinicians made so long ago with the basic assumption that we can replace a defective gene to treat disease.  These studies I believe have revitalized the field for both academia and industry, legitimized gene therapy as a practical approach to treat disease, and paved the way for a new generation of researchers, such as myself, to develop new therapies.

In your opinion, what are the greatest areas of need which must be addressed to ensure continued progress in this field?

From my personal experience in the field I would say standardization presents a great challenge to continued progress.  So this is a pretty general problem, for example if lab A makes a vector and lab B makes the same vector the odds are that each step of the process (such as production, processing, purification, and tittering) is different enough to actually give two different vector preps.  So while individual labs may be consistent with their vectors it poses a problem for others trying to reproduce results or use similar vectors for other applications. For example depending on the vector, there can be up to four to five different means to determine vector titer.  Some effort has been made to create a banked standard for AAV vectors, but it is limited for specific transgenes or promoters.  Another example from AAV can be seen in the purification strategy that can result in different ratios of empty to full AAV capsids.  While this may not have much of an impact in naive animals or humans, there is evidence that empty capsids can act as a sponge/decoy in the presence of AAV neutralizing antibodies, thus administration of the same titer of vector can result in a measured difference in transgene expression.  These issues can also be found in other vector systems.



Janaiah Kota, PhD


Questionnaire

Tell us a little about why you decided to get involved in the field of gene and cell therapy as well as with the Society.

In 2006, while I was working as a post-doctoral researcher in the Department of Horticulture and Crop Science at The Ohio State University, I read a new article published in the Columbus Dispatch on a Gene Therapy Clinical Trial for Duchenne Muscular Dystrophy at Nationwide Children’s Hospital led by Dr. Jerry Mendell, based on pre-clinical studies from Drs. Jude Sumulski and Xiao Xiao’s group. I knew that Duchenne Muscular Dystrophy is one of the most devastating diseases in young boys and that it has no effective cure. In the next few months, I educated myself about gene and cell based therapies and their potential applications in developing treatments for a wide range of human diseases. During this process, I came across some promising pre-clinical studies for other genetic diseases like childhood blindness and hemophilia. As I learned more, I was intrigued by the great promise that gene therapy presents, and I came to believe that restoring the functional copy of a defective gene is the best approach to cure various human diseases and reduce the suffering of afflicted individuals. This realization motivated me to switch my career path from Plant Sciences to Biomedical Sciences. Because of its translational nature, Gene Therapy is the most relevant biomedical field to my graduate training in applied aspects of Plant Sciences/Agriculture. On the whole, both fields have many similarities: transgenics vs. gene product; field trial vs. clinical trial; USDA vs.FDA. These similarities gave me confidence that there was a fair chance for me to succeed in the gene therapy field and allowed me to approach Dr.Mendell for a post-doctoral position in his laboratory. Since then, I have been actively engaged in gene therapy research, and affiliated with ASGCT as a member, active presenter at the annual meetings, and more recently, an abstract reviewer.

How has ASGCT advanced your scientific and/or career development?

ASGCT has been greatly instrumental in shaping my career path. Annual meetings provide me a solid platform to present my research findings, learn about advances in the field, and interact with my peers. Special sessions on funding opportunities and career development are extremely helpful to me. Additionally, the society’s webpage has a lot of information relating to Gene Therapy, which helped me gain knowledge in the early years of my career.

Have you had any mentor(s) that has/helped you in furthering your research?

My former mentor, Dr. Jerry Mendell, has been very supportive throughout my post-doctoral career. He has influenced me in many ways both at a professional and personal level. He taught me the critical components of translational research and the necessary precautions to be taken to rapidly translate basic research findings to the clinic. His unyielding commitment to curing Duchenne Muscular Dystrophy is an inspiration, and his determination and work ethic has had a profound impact on me personally

In addition, my co-mentor, Joshua Mendell, was an instrumental figure in advancing my research in the cancer-microRNA field, which is now my chosen career path.

Although, I did not have a formal mentoring committee, I had an informal mentoring committee composed of ASGCT members K.Reed Clark, Brian Kaspar, Scott Harper, and Zarife Sahenk, who have been a constant support to advance my research and career. In addition to my formal mentors, Dr. Harper advised me on many aspects while applying for faculty positions.

What did you think of your involvment as an Abstract Reviewer for ASGCT? Did this exposure to another aspect of the Society benefit you in any way?

It has been a great opportunity to serve as an abstract reviewer for ASGCT and evaluate the work of my colleagues. It has helped me to further my knowledge and learn about new approaches to address scientific problems. It has also enabled me to interact with and understand the viewpoints of senior scientists in the field. It was certainly a great learning opportunity for me as an early stage investigator.

What advice would you give to students or post doctoral fellows who are new to the field and/or the Society

Gene and cell therapy has tremendous potential to cure various human diseases.  In addition to their clinical applications, viral and non-viral vectors will serve as great tools in addressing fundamental biological questions.

Make your career plans well in advance. Know where you want to be in the next five years and discuss your plans with your mentor. Participating in career development opportunities and having a mentoring committee through your society will always be beneficial. In the lab, involving yourself in a secondary project in addition to your primary project will help you to be more competitive by having more publications when you are ready to apply for jobs. Also, writing a career advancement grant will always help in gaining valuable grant writing experience.



Katherine Excoffon, PhD


Questionnaire

Briefly describe your current research interests.

My lab is currently focused on the cellular mechanisms that regulate virus receptor expression and accessibility in polarized epithelia. We are primarily focused on the coxsackievirus and adenovirus receptor (CAR) and have found that the susceptibility of an epithelium to virus infection can be modulated by several external and internal factors. We are also using directed evolution to develop novel AAV vectors to target specific cell types. al and pre-clinical trials focused on new conditioning modalities and transplantation of purified or gene-modified HSC

When and why did you first develop an interest in gene and cell therapy

I was thinking about gene and protein therapy before I even knew what genes and proteins were. Having an older sister with Rubinstein-Taybi syndrome shaped my thoughts about what was “normal” and what caused things to be “abnormal”. I have always believed that the discovery of how to change the abnormal back to normal was only a matter of investigation. As I learned about genetics and molecular biology, I dreamt of ways to “cure” not only my sister, but also others with genetic disabilities. I was thrilled when I had the opportunity to join the lab of Dr. Michael Hayden at UBC in Vancouver in 1995 as a PhD student to investigate gene therapy for lipoprotein lipase deficiency in a feline model of this disease. I was first to put the LPL variant – the gene has now been approved as the first human clinical gene therapy (Glybera) – into an adenovirus vector and demonstrates its amazing efficacy. It was natural for me to join a Society of scientists that shared my dreams. I attended the very first Society meeting back in 1998 and have attended many of them since.

In what ways do you feel the ASGCT has played a role in your scientific and career development?

ASGCT has always been a source of cutting-edge information and a wonderful platform to present research. However, the best career development event was the new mentoring event organized by Dr. Matt Weitzman. As a new faculty member, I could have been an early career mentor, what I really needed was access to senior scientists in the field who might be willing to be mentors for me. Until this point, I had felt the Society was very stratified and it was difficult as a postdoc/research scientist to be active within the Society and meet senior faculty in other fields. For the first time I met and had wonderful concise discussions with Drs. Maria Castro, Mavis Agbandje-Mckenna, Jeff Chamberlain, John Rossi, and Renier Brentjens. Both Drs. Castro and Agbandje-Mckenna have provided ongoing mentoring invaluable to my career development.

In light of your accomplishments, what advice would you offer to your ASGCT colleagues with respect to research and/or career development?

Believe the words of Eleanor Roosevelt – “the future belongs to those who believe in the beauty of their dreams.” Forget about the “traditional paths” – they don’t exist. As I get to know more scientists, no one is truly “traditional” anyways. Instead, tread a path that allows you to believe and achieve your scientific dreams, while at the same time allows you to keep your core values and achieve your life dreams. Mentoring is the surest way to get to know yourself and keep life and science in balance.

How do you like to pass the time outside of work?

Family time is precious and a great deal of time is spent at soccer fields or helping with school. However, I have recently started to play ice hockey - a great way to relieve stress!



Agnieska Czechowicz, MD, PhD

Current Position: Resident/Postdoctoral Fellow


Questionnaire

Briefly describe your current research interests.

I am currently focused on better understanding the basic biology of hematopoietic stem cells, and translating insights from our work to first improve the field of bone marrow transplantation, and ultimately other regenerative efforts.

The main barrier to more widespread use of bone marrow transplantation is the toxicity of the procedure; which is largely due to the toxic conditioning regimen necessary for HSC engraftment and the graft versus host disease that often results from engraftment of a non-purified allogeneic graft.  I have been interested in eliminating both of these risks by developing strategies to increase engraftment of purified allogeneic or gene-modified autologous HSC.

In particular, I am currently studying novel HSC markers and signaling proteins and developing ways to perturb those in order to deplete host HSC and/or enhance engraftment of newly transplanted stem and progenitor cells.  In addition, I continue to collaborate with colleagues to develop clinical and pre-clinical trials focused on new conditioning modalities and transplantation of purified or gene-modified HSC

Briefly describe how you reached your current position (educational background)

I became interested in biology at an early age, and worked in a number of academic and industry settings throughout high school and college, including the University of Minnesota and the National Institutes of Health.  Ultimately I honed my scientific interests and became passionate about translational cell and gene therapy and intending to bridge the divide between basic science and clinical medicine, I decided to do an MD/PhD at Stanford University.

Given my desire to develop a strong foundation in stem cell biology, I did my graduate work on hematopoietic stem cells with Prof. Irv Weissman.  There I showed that one of the greatest barrier to HSC transplantation is the availability of the hematopoietic stem cell niche and developed multiple novel approaches to eliminating this toxicity including developing an anti-c-kit monoclonal antibody based conditioning regimen and proving efficacy in immunodeficient mouse models and human xenograft models.

Together with my colleagues, we have partnered with the California Institute of Regenerative Medicine and pharma to develop a similar human-grade reagent we intend to trial in patients beginning next year.  Additionally, as part of my education, I completed the Stanford University Institute of Entrepreneurship and interned at Third Rock Ventures, a unique firm that works on launching and building transformative biotech companies.

I am now completing pediatric residency training at Boston Children’s Hospital/Boston Medical Center Combined Residency Program and will begin a fellowship in pediatric hematology/oncology and transplant at the Dana-Farber Cancer Institute and Boston Children's Hospital program next year.  Simultaneously I have been continuing my research efforts as a postdoctural fellow in the laboratory of Prof. Derrick Rossi, where I have a number of interesting new projects, and continue to advise Third Rock Ventures and a number of their portfolio companies.

When and why did you first develop an interest in gene and cell therapies?

I have long been interested in regeneration and in the repair of diseased organs, and believe current treatment modalities have been unable to successfully and fully combat this challenge.  I believe with continued improvement gene and cell therapies have the widespread ability to address these illnesses.

In particular, as a pediatrician I see a number of horribly grievous diseases with significant organ dysfunction where small molecules and biologics have not been sufficient.  I would love to not just treat these patients, but ultimately long-term cure them and believe this can only be achieved by gene and cell therapy.

My specific research focus has been in hematopoietic stem cell biology; as this is the oldest, most-accessible and best-defined of stem cells.  I feel that much of what we learn from this system can then be rapidly translated to our understanding of other stem cell systems, gene-therapy and ultimately regeneration

In your opinion, what are the greatest areas of need which must be addressed to ensure continued progress in this field?

Most importantly people must learn how to work together, to truly fully collaborate, and learn build on each other’s progress for this field to be successful.  Cell and gene therapy is significantly more complex than other treatment modalities, and we need all the smartest brains and hands on deck here.  Individuals, institutions and organizations need to put their egos and greed aside and work together if we are to ultimately create the best therapeutics at the most rapid rate to help the most patients.

There have been many great advances in this field over the years, but many challenges still remain before cell and gene therapy becomes widespread.  These are not trivial projects, and each have many complex components.  It is unfortunate that so much work has been done in isolation and so frequently the same pieces continue to be re-invented.  The field needs to continue to work together to optimize each of the components of cellular and gene therapies, and carefully and cautiously develop and implement the therapies so that they are both safe and efficacious.  This applies broadly to everyone involved in the field including scientists, clinicians, regulators, intellectual property agents, patient advocacy groups, and all those with a vested interest in seeing this become successful.

How do you like to pass the time outside of work?

 I enjoy spending time with passionate individuals who are trying to make a difference in the world.  In addition, I love traveling and exploring different cultures that give me a unique outlook on life, as well as taking care of patients and their families.



Barbara K. Smith

Current Position: Research Assistant Professor


Questionnaire

Briefly describe your current research interests.

My career objective is to promote rehabilitation and respiratory motor recovery for patients with ventilatory muscle weakness and respiratory compromise. In the presence of incurable neuromuscular diseases, regenerative therapies hold great promise for restoring independent ventilation. I am especially interested in combining traditional rehabilitation interventions with gene and cell therapies, to promote a functional restoration of the target tissue.

Briefly describe how you reached your current position (educational background)

I spent >10 years in the clinical care and study of patients who needed support from mechanical ventilators. This work led to my interest in using targeted exercises to rehabilitate respiratory muscles weakened from critical illness and inactivation by the ventilator, which inspired a departure from the clinic to academia. After concluding graduate studies in respiratory muscle biology, I was then appointed to the K12 Rehabilitation Research Career Development program at University of Florida. As part of this program, I have the good fortune to be mentored by Dr. Barry Byrne, an international expert in cardiopulmonary function and pioneer in gene therapy for neuromuscular disease.

What do you view as your greatest scientific achievement to date?

It has been a privilege to work with Dr. Byrne and the entire study team at University of Florida, as a member of a phase I/II clinical trial of AAV1-CMV-GAA intramuscular gene therapy to the diaphragm in ventilator-dependent children with Pompe disease. It has been especially rewarding to work with the amazing patients and families who dedicated their time to this innovative project.

In your opinion, what are the greatest areas of need which must be addressed to ensure continued progress in this field?

These are truly exciting times in gene and cell therapy, as more therapeutic products approach the clinical trial development phase. A crucial element to a clinical trial of gene and cell therapy is the validation of sensitive and reliable outcome measures. Our ability to detect clinically meaningful changes to breathing will be essential to determine the efficacy of proposed therapeutic products and could influence the regulatory process for future applicants.

In what ways do you feel the ASGCT has played a role in your scientific and career development?

ASGCT has been a tremendous advocate to junior investigators. The organization provides an extensive center of educational resources, with a number of programmatic, award, mentorship, and networking opportunities to promote career growth and development. I have found the mentorship and networking experiences to be particularly useful.



Renzhi Han
 
Current Position: Assistant Professor

Questionnaire

Briefly describe your current research interests.

My current research interests are to study the molecular mechanisms underlying muscular dystrophy (a group of genetic diseases affecting skeletal muscle) and develop gene/cell-based therapeutic strategies for treating these devastating diseases.

Briefly describe how you reached your current position (educational background)

After graduating with a B.S. in Physiology and Biophysics in 1998 from Peking University in China, I was awarded an International Postgraduate Research Scholarship from Australia to pursue my PhD training in muscle physiology and disease with Drs. Anthony J. Bakker and Miranda D. Grounds at the University of Western Australia. During my PhD studies, I developed my interest in muscular dystrophies, a group of genetic diseases characterized by progressive skeletal muscle weakness and wasting. My interest in muscular dystrophies brought me to the laboratory of Dr. Kevin P. Campbell at the University of Iowa for my postdoctoral training in 2003. As a postdoctoral fellow in Dr. Kevin Campbell’s laboratory, I studied the mechanisms that underlie compromised membrane integrity in muscular dystrophies. In September 2009, I began my first faculty position as an Assistant Professor at Loyola University Chicago Health Science Division.

When and why did you first develop an interest in gene and cell therapies?

I started to develop an interest in gene and cell therapy during the second year of my PhD when I learned about muscular dystrophy. As with many genetic diseases,  muscular dystrophy patients suffer without effective treatments.

What, in your opinion, marks the greatest advance to date in the field of gene and cell therapy and why?

During the past decades, scientists have made tremendous progress in  gene cloning, expression manipulation (i.e. RNAi), and stem cell technology. What impresses me the most is the recent advance in genome editing technology. This may open up a new era of gene and cell therapy in combination with advances in induced pluripotent stem cells.

In your opinion, what are the greatest areas of need which must be addressed to ensure continued progress in this field?

Off-target activity, low efficiency of genome editing, and gene delivery technology are three important areas among many others that should be addressed for moving genome editing technology to therapeutic applications.

How do you like to pass the time outside of work?

 I have a 8-year-old daughter and my wife is pregnant with our second baby. Outside of work, I spend a lot of time with my family, walk/bike for 45 minutes every day, take my daughter to school and piano lessons, and play games with her. Trust me, my daughter has the energy to use up all my time outside of work.



Drew Deniger
 
Current Position: Graduate Research Assistant

Questionnaire

Briefly describe your current research interests.

My current research interests are primarily focused on developing cellular therapies for cancer patients. This is generally divided into two main projects. The first is to harness the inherent anti-tumor immunity of gamma delta T cells to target a broad range of tumor cells. There are several different lineages of T cells, and we have developed a novel method for the expansion many of these T cell subsets in one cellular therapy product. Polyclonal gamma delta T cells will recognize multiple tumor ligands and, therefore, maximize treatment efficacy. The second main aim is to re-direct the specificity of T cells to tumor-associated antigens (TAA), e.g. CD19 and Receptor tyrosine kinas-like Orphan Receptor-1 (ROR1), with chimeric antigen receptors (CARs). Both gamma delta T cells and the more prevalent alpha beta T cell subset (~95% of peripheral T cell pool) are used for studies with CARs, which are expressed in T cells following electro-transfer of plasmid DNA and stable integration into the genome through Sleeping Beauty transposition. Killing and pro-inflammatory cytokine production towards TAA demonstrated re-directed specificity of the T cells towards tumors. There is great hope that the promising achievements in these projects will translate into efficacy in the clinic.

When and why did you first develop an interest in gene and cell therapies?

The first time I was exposed to cell therapy was in my “Translational Research” course at the University of Texas Graduate School of Biomedical Sciences at Houston. Dr. Cooper, who is now my PhD advisor, taught us about chimeric antigen receptors (CARs) and adoptive cellular therapy. The strategy just made sense to me – that is to use the body’s system for eliminating damaged cells to kill tumor cells. Now that I have 5 years of testing cell therapies myself in Dr. Cooper’s lab, I am convinced it is one of most effective options for cancer treatment.

In what ways do you feel the ASGCT has played a role in your scientific and career development?

ASGCT has certainly played a significant role in my early career development. My first T cell immunotherapy paper was published in the ASGCT journal Molecular Therapy. This has assisted my ability to (1) write my dissertation and (2) find and accept a post-doctoral fellowship position. The 14th Annual ASGCT meeting is where I first presented the data later published in Molecular Therapy, and it was where much interest was generated about the project and motivated me to forge ahead towards publication. More specifically, specific technical guidance and pre-peer review advice greatly assisted my efforts to complete the project. I will attend the 16th Annual ASGCT meeting as the result of an ASGCT travel award, which was crucial to my ability to attend. As the work that I will present there is on the verge of publication, it is anticipated that guidance and insights will help the current project as it did for the one that was published after the 14th Annual meeting. Thus, the past and current support of ASGCT has been a key component of my scientific and career development.

Where do you see yourself 10 years from now?

Ten years from now I hope to have finished my post-doctoral fellowship and obtained a more permanent position where I can continue to make T cell immunotherapies. This could either be in the traditional academic route at a biomedical research institution or in the private biomedical research industry. In the end, my primary goal is to make discoveries or developments that will impact patients in the immediate future.

How do you like to pass the time outside of work?

Outside of work, I most often exercise (running, lifting weights, and play soccer) and watch movies at home. Netflix is one of my favorite amenities. We have a golden retriever, so we play catch (more than one tennis ball is key because she does not like letting go once retrieving) and, more recently, soccer (she’s not that good but let’s give her a break). The Houston climate allows for excellent plant growth, so I maintain a garden with tomatoes (cherry and heirloom), peppers (jalapeno, banana, and cayenne), herbs (parsley, sage, rosemary, thyme, etc), and flowers (my favorite growing currently is bouganvilla). Houston also has excellent restaurants, so my wife and I try as many places as time and cash-flow can afford.



Sourav Choudhury
 
Current Position: Graduate Student

Questionnaire

Briefly describe your current research interests.

My current research interests involve screening of DNA shuffled AAV libraries to screen for novel vectors that are capable of transducing specific cell populations of the central nervous system.

When and why did you first develop an interest in gene and cell therapies?

 In 2009, I joined the lab of Miguel Sena-Esteves at the University of Massachusetts Medical School as a doctoral candidate, where I am currently. Our lab focuses on gene therapy of central nervous system disorders, particularly using AAV vectors, and this is where I picked up my interest in development of better AAV vectors for gene therapy.

What, in your opinion, marks the greatest advance to date in the field of gene and cell therapy and why?

In terms of total impact on the field, Paul Berg's attempts to transfer lambda bacteriophage DNA to monkey kidney cells using SV40 virus was perhaps the most important as it was one of the first attempts of using viral vectors for gene therapy. It also led to the development of the 'cut-and-splice' method of cloning recombinant DNA used ubiquitously to this day and in addition led to a public debate on science policy and regulation of biotechnology research, culminating in the guidelines developed during the Asilomar Conference. More recently, the development of AAV vectors for gene transfer was very important. These are replication-defective, do not integrate into the host genome and have a low immunogenic profile. These are almost every characteristic of the ideal viral vector.

In your opinion, what are the greatest areas of need which must be addressed to ensure continued progress in this field?

Understanding vector transduction of cells at a molecular level (such as identification of novel receptors/co-receptors on cell surface for vector binding and endocytosis) to develop vectors targeted to a more specific cell population is one such field. Rational cell type-specific promoter/enhancer element design for transgenes is another. Modulating host responses to vector, such as reducing (or enhancing, as the case may be) the immumogenicity of vector or transgene is a third area.



Luca Biasco, Ph.D.
 
Current Position: Post Doctoral Fellow

Questionnaire

Briefly describe your current research interests.

My current research interests are in the area of retroviral/lentiviral vector integration studies in gene therapy clinical trials. In particular, my research projects are based on the exploitation of gene therapy patients’ “integrome” as a unique barcode-based model to study hematopoietic system biology in vivo at single clone level in humans.

When and why did you first develop an interest in gene and cell therapies?

I graduated in Biotechnology at Alma Mater Studiorum University of Bologna in 2003 and worked for 2 years as fellow on pediatric leukemias. During this period I spent 2 months at the National Institutes of Health (NIH) in Bethesda studying the impact of decitabine and valproic acid on acute myeloid leukemia cells transcriptome by custom microarrays.

My first contact with gene therapy (GT) was in 2005 when I moved from Bologna to Milan to start a PhD in the group leaded by Prof. Alessandro Aiuti at HSR-TIGET. By that time gene therapy field was in jeopardy due to the reports of the first cases of leukemias originated from insertional mutagenesis in GT clinical trials for severe combined immunodeficiencies (SCID). During my first years at TIGET I was able to assess the safety of retroviral gene therapy for ADA-SCID by retrieving integration sites and studying their distribution in vivo in treated patients. I also shed light on vector-host interactions uncovering a target-cell dependent IS distribution of retroviral vectors and the genetic and epigenetic factors influencing the cell-specific genomic localization of proviral insertions.

What, in your opinion, marks the greatest advance to date in the field of gene and cell therapy and why?

One of the major advances in gene therapy field achieved in the past 5 years is represented by the design and the successful clinical exploitation of a new generation of retrovirus-based vectors that combine strong transduction efficiency with a finely regulated transgene expression and a safer insertional profile, able to overcome the limitation of the first vector platforms.
  Question 6 txt: One of my favorite quote says: ” Big data is like teenage sex: everyone talks about it, nobody really knows how to do it, everyone thinks everyone else is doing it, so everyone claims they are doing it”

The next years will see an increasing impact of deep sequencing for the screening of novel gene-transfer technologies and the follow-up of gene therapy clinical trials. There will thus be an increasing demand for a proper integration of bioinformatics and biology with the development of specific in silico platforms for data manipulation and analysis. However, gene therapist should at the same time become educated to preserve their hypothesis-driven approach to biological questions in order to avoid the risk of “datafication” and correlation/causation distortions inherent to the potential overflow of data from deep sequencing technologies.

In light of your accomplishments, what advice would you offer to your ASGCT colleagues with respect to research and/or career development?

Commitment and endurance are always the key words. However, I also believe that research is still about having fun and enjoying the discovery process. Whatever is your career plan I suggest you to always keep alive the young spirit of wondering and speculating that makes this job unique.

How do you like to pass the time outside of work?

During my free time I love doing sports on a daily basis like biking and running, weekly like soccer and seasonally like snowboarding and surfing. I also love music and I own an acoustic and an electric guitar that I enjoying playing whenever I can.



Charles M. Brunicardi, MD
 
Current Position: Moss Professor and Vice Chair of Surgery

Questionnaire

Briefly describe your current research interests.

My principal research interests are in the areas of pancreatic physiology, differentiation and pancreatic cancer and that the transcription factor PDX-1 plays a key role in determining cell lineages in the pancreas also plays a pro-oncogenic role in the development of pancreatic cancer.

Briefly describe how you reached your current posiiton (educational background)

 I am a gastrointestinal surgeon-scientist who trained at SUNY Brooklyn Health and Science Center, Brooklyn, during which time I did a three year research fellowship in pancreas physiology. As an assistant professor, I became a member of the CURE: DDRC from 1989 to 1995 to study somatostatin receptors and then was recruited in 1995 to Baylor College of Medicine in Houston, Texas as George Jordan Professor and Chief of General Surgery. In 1999, Brunicardi became DeBakey/Bard Professor and Chairman of the Michael E. DeBakey Department of Surgery at Baylor and held that leadership position for 12 years. In 2011, Dr. Brunicardi rejoined the UCLA faculty as Moss Foundation Chair in Gastrointestinal and Personalized surgery, Professor and Chief of the Santa Monica-UCLA General Surgery Group and a Vice Chair of the Department of Surgery for Surgical Services at Santa Monica-UCLA Medical Center. At the same time, Dr. Brunicardi also rejoined the CURE: DDRC where his laboratory is located.

When an