Curtis Pickering, Ph.D.
Department of Head and Neck Surgery - Research
MD Anderson Cancer Center
TRIUMPH Fellow: 2009-2011
TRIUMPH Mentor: Jeffrey Myers, M.D., Ph.D.
Dr. Pickering earned his B.S. in Biochemistry & Molecular Biology from Michigan State University. He pursued his graduate degree at University of California - San Francisco, where he received his Ph.D. in Cell Biology for his research aimed at understanding the early events in breast carcinogenesis by studying the consequences of p16INK4a inactivation in primary human mammary epithelial cells. He joined the TRIUMPH Postdoctoral Fellowship in 2008 and completed his research on the integrated genomic analysis of head and neck squamous cell carcinoma under the mentorship of Dr. Jeffrey Myers at MD Anderson Cancer Center, where he later earned a faculty position. Dr. Pickering helped lead the first whole exome and integrated genomic studies of head and neck cancer and participated in the subsequent and larger-scale head and neck cancer genomics project from The Cancer Genome Atlas (TCGA).
As an Assistant Professor appointed in the Department of Head & Neck Surgery at MD Anderson, Dr. Pickering continues his research on the translational genomics of head and neck cancer. His research goal is to improving the treatment of head and neck cancer by understanding the genomic alterations that drive the disease. His translational research laboratory utilizes patient samples, patient study data, computational tools, functional genomics, and relevant in vitro and in vivo model systems to characterize genomic alterations and understand their relevance to tumor progression and treatment response. By integrating data across platforms and models their studies span nearly the entire translational spectrum from bedside to bench and back. He now serves as a faculty mentor for the CPRIT Research Training Program.
Dr. Pickering explains “For me the most eye-opening part of the TRIUMPH program was the clinical rotations. They taught me how to communicate and work with physicians and design better translational studies. It was very important for me to see first-hand how patients are treated by physicians. First, I learned the uniqueness of each patient and their own individual disease and treatment path. This demonstrated that any study involving patients will have much more variability than a lab-based study, and there are many more uncontrolled variables in the clinic, so it is inherently more difficult to study patients and patient samples. Second, I learned about the priorities and time-constrains of physicians. Their top priority is the patient, not my research project or even their own research project. Additionally, their options in treating that patient are often limited by practical and ethical concerns. In many instances, the best experimental design cannot actually be performed because the patient has to be treated in a certain way that is in compatible with the research study plan. The ideal translational research project is not only scientifically sound but also clinically feasible, relevant to the treatment of your specific disease, and has a clear translational path to improving patient care. Lots of interesting studies are not realistic or translational.”
Sherry Yen-Yao Wu, Ph.D.
Senior Lecturer (Assistant Professor equivalent), Faculty of Medicine
School of Biomedical Sciences
University of Queensland (Australia)
CPRIT TRIUMPH Fellow: 2011-2015
CPRIT TRIUMPH Mentor: Anil Sood, M.D.
Dr. Wu received her Bachelor's in Pharmacy and her Ph.D. from University of Queensland in Australia. Her Ph.D. work focused on developing novel delivery systems for E6 and E7 targeted siRNA for cervical cancer therapies and involved developing a novel approach to formulate liposomal nanoparticles as well as studying the effects of silencing E6/7 on cervical cancer growth both in vitro and in vivo. Dr. Wu joined MD Anderson Cancer Center in 2011 as a Postdoctoral Fellow and led a project focused on understanding the role(s) of non-coding RNAs in tumor angiogenesis and developed novel therapeutic approaches to inhibit tumor angiogenesis. In collaboration with an industry partner, she also developed a novel method to significantly enhance the potency of siRNA therapeutics in ovarian cancer. Dr. Wu has a robust and prolific publishing record from her time at MD Anderson and in the CPRIT TRIUMPH Program.
Following her TRIUMPH Postdoctoral Fellowship, Dr. Wu was appointed Research Assistant Professor at MD Anderson, where she continued her work in ovarian cancer. She recently moved home to her native Australia, where she directs the Cancer Therapeutics laboratory and serves on the faculty at University of Queensland. Her research interests focus on developing effective strategies for the detection and treatment of ovarian and breast cancers and to translate these research findings into the clinic. Her current focuses are in harnessing the immune system for cancer therapy, tumor-targeted drug delivery systems, and examining the role(s) of exosomes in cancer progression. Through her active collaboration with clinicians in local hospitals, she continuously addresses research questions that matter the most for cancer patients.
Dr. Wu believes that her participation in the TRIUMPH program has been instrumental in her career success. She explains "The TRIUMPH program has helped me tremendously in terms of shaping up my career path. I have learned so much from the program. This includes knowledge related to clinical translation that I would not have gained if I did a normal, traditional postdoctoral fellowship. TRIUMPH program also significantly expanded my professional network and allowed me to establish new research collaborations with physicians to solve clinically important questions. The support I obtained from the TRIUMPH program did not stop when I finished the program. The TRIUMPH program very much focuses on the fellows' career development and I would not be where I am today if I were not a TRIUMPH fellow. TRIUMPH cares about each fellow's development and provides all the resources and support necessary to allow all fellows in the program to reach their maximum potential."
Marco Napoli, Ph.D.
Department of Molecular Oncology (Dr. Elsa Flores Lab)
Moffitt Cancer Center
CPRIT TRIUMPH Fellow: 2014-2016
CPRIT TRIUMPH Mentor: Elsa Flores, Ph.D.
Dr. Napoli earned his B.S. in Biotechnology from the University of Palermo and his M.D. and Ph.D. in Molecular Biomedicine from the University of Triste in his home country of Italy. During his Ph.D., Dr. Napoli contributed to several projects unveiling the mechanism of action of many breast cancer-promoting factors impinging on the p53 family. His work led to the identification of an innovative method for the prognosis of breast cancer (European Patent Office #2012738204). Specifically, he investigates the mechanisms underlying mutant p53 gain of function, focusing on factors that might link cancer-related signaling with mutant p53 activity. He demonstrated that this link is provided by an enzyme, the prolyl isomerase Pin1, which enhances tumorigenesis in a Li-Fraumeni mouse model and cooperates with mutant p53 in Ras-dependent cell transformation. In human breast cancer cells, Pin1 promotes both mutant p53-dependent inhibition of the anti-metastatic factor p63 and the induction of a mutant p53 transcriptional program to increase tumor aggressiveness. Dr. Napoli also identified a group of 10 genes (the "Pin1/mutant p53 signature") that is associated with poor prognosis in breast cancer and, in a cohort of patients, Pin1 over-expression influences the prognostic value of p53 mutation. Considering that TP53 mutation is more frequent in tumors with higher risk of recurrence such as triple negative cases and that some of the Pin1/mutant p53 signature genes are over-expressed in triple negative breast cancers, these findings carry therapeutic implications for these kinds of cancers and possibly also for other tumors bearing mutant p53 and high levels of Pin1.
In 2014, Dr. Napoli joined the TRIUMPH program under the mentorship of Dr. Elsa Flores, where he studied micro-RNAs that mediate therapeutic efficacy of HDAC inhibitors in cancers, work that earned him a Cancer Cell publication in 2016. The goal of
his project as a TRIUMPH postdoctoral fellow was to identify small molecules able to target ΔNp63, an oncogenic member of the p53 family that acts as a dominant negative towards its family members, thus effectively treating ΔNp63-addicted tumors. By
performing a chemical library screen, Dr. Napoli identified HDAC inhibitors (HDACi) as a class of agents that reduce ΔNp63 protein stability through the E3 ubiquitin ligase, Fbxw7. This in turn decreases the levels of the ΔNp63 direct target gene, DGCR8, and the maturation of a specific set of miRNAs critical for the function of HDACi. Notably, the viability of cancer cells with p53 mutations and their ability to form tumors in vivo were curbed by treatment with either HDACi or inhibitors of the identified miRNAs, let-7d and miR-128. Importantly, these results demonstrated that: 1) Fbxw7 is a crucial marker predicting
responsiveness of human tumors to HDACi-based therapies; and 2) tumor resistance to HDACi can be overcome by targeting let-7d and miR-128. Dr. Napoli moved to Moffitt Cancer Center with the Flores laboratory in 2016.
Dr. Napoli is currently a postdoctoral fellow in the laboratory of Dr. Elsa Flores at the Moffitt Cancer Center (Tampa, FL, USA). He is currently investigating the regulation of regulation of long non-coding RNAs (lncRNAs) by the tumor and metastasis suppressor, TAp63, which is a p53 family member and a p63 isoform. Loss of TAp63 leads to highly metastatic breast adenocarcinomas in mice and correlates with high-grade breast cancers in humans. By performing a mouse-human cross-species analysis, he identified two TAp63 regulated oncogenic lncRNAs whose levels correlate with breast cancer progression and are higher in invasive breast cancers expressing mutant p53. Notably, Dr. Napoli demonstrated that targeting these lncRNAs or their downstream effectors is effective in treating murine models of metastatic breast cancer. He is now evaluating the oncogenic roles of these lncRNAs and their effectors in other tumor types.
Of our program, Dr. Napoli says "The TRIUMPH program gave me the great opportunity to deepen my knowledge of translational cancer research and to establish collaborations with several clinicians both at MD Anderson Cancer Center and at Moffitt Cancer Center, whose invaluable insights have helped me in guaranteeing that my findings may have a positive impact for the management of cancer patients."
Dr. Napoli Publication History:
PUBMED Author Link
Aaron Orozco, Ph.D.
Senior Research Scientist, Department of Pediatric
MD Anderson Cancer Center (Houston, TX)
CPRIT TRIUMPH Fellow: 2011-2012
CPRIT TRIUMPH Mentor: Robert Bast, Jr., M.D.
Dr. Orozco received his B.Sc. in Microbiology and Molecular/Cellular Genetics from California State University at Long Beach (Long Beach, CA) and continued on to earn his Ph.D. from Baylor College of Medicine (Houston, TX) in Immunology. He joined the TRIUMPH program in 2011 under the mentorship of Dr. Robert Bast, Jr. and studied VEGF, IGF, and IL-8 as novel therapeutic targets in tumor cell dormancy in ovarian cancer.
Dr. Orozco currently serves as Senior Research Scientist at MD Anderson Cancer Center, where he leads flow cytometry operations to characterize and monitor CD19- and CD33- CAR T cells for clinical trials. Of his experience in the TRIUMPH program, he says "The TRIUMPH program helped me to understand the gap between basic research and clinical needs. I was honored and excited to have the opportunity to perform translational research that could potentially be applied to our cancer patients."
Stephanie Puig, Ph.D.
Research Assistant Professor
University of Pittsburgh, Department of Anesthesiology
CPRIT TRIUMPH Fellow: 2015
CPRIT TRIUMPH Mentor: Howard B. Gutstein, M.D. (now at University of Pittsburgh)
Dr. Puig earned her Bachelor's in Life Science and Biology with high honors from Universite Paul Sabatier and her Master's degree in Life Science with a neuroscience focus from Universite Pierre et Marie Curie in France. She received her Ph.D. in Neuroscience and Neuropharmacology from Universite Paris Descartes in Paris, France under the mentorship of Dr. Florence Noble. Her doctoral research focused on analyzing the behavioral, neurochemical, and cellular effects of cocaine in the brain. Dr. Puig's work and hypothesis were inspired by observations from clinicians working in collaboration with her, who suggested that the treatment of addiction to cocaine should be adapted according to the pattern of cocaine consumption of each patient. Dr. Puig's work lead to three major discoveries:
1) Different patterns of administration of cocaine lead to very different behavioral, neurochemical and cellular modifications in the brain of rats.
2) She revealed the existence of a neurochemical memory in the brain, related to the pattern of administration of cocaine. This neurochemical memory is characterized by changes in dopamine levels (using in vivo microdialysis) in the nucleus accumbens (a core nucleus of the reward system), at the moment when rats were used to receive the drug.
3) The pattern of administration also induces different changes in the levels of Brain-derived Neurotrophic Factor (BDNF) in the blood and in the brain structures involved in addiction. Variations of BDNF in the blood correlate to variations in the brain which suggested that the BDNF could be a good biomarker for addiction.
Dr. Puig continued her interest in neuroscience and opioid research as a Postdoctoral Fellow in the laboratory of Dr. Howard B. Gutenstein in 2013 and joined the TRIUMPH program in early 2015. Her postdoctoral research focused on understanding the involvement of growth factor signaling in opioid-mediated analgesic tolerance. They showed that Imatinib, a platelet-derived growth factor receptor beta (PDGFR-β) inhibitor, could completely prevent and reverse morphine-mediated analgesic tolerance. Importantly, they discovered that the PDGFR-β ligand, the platelet-derived growth factor type B (PDGF-B) is necessary and sufficient to cause morphine tolerance. Blocking the release of PDGF-B completely prevents tolerance and administration of PDGF-B causes tolerance in rats that had never received morphine before.
Her work extended these findings to other growth factors (Epidermal Growth Factor (EGF), Sonic Hedgehog (SHh) and Vascular Endothelial Growth factor (VEGF)). Using the most advanced methods in microscopy and neuroanatomy, she was able to characterize the presence of these growth factors and their receptors in the neuronal network that conveys pain, morphine analgesia and tolerance. Using a behavioral and a pharmacological approach, she provided evidence that blocking the signaling of these proteins can robustly preserve morphine efficiency over time and therefore block tolerance. Importantly, Dr. Puig also found that growth factors signaling is a core mechanism for tolerance to other opioids used in the clinic. Noteworthy, several growth factor inhibitors that she showed block tolerance are FDA approved and are commonly used as chemotherapeutic agents for the treatment of cancer. These drugs are already known to be tolerated by humans, which means that they could be rapidly approved for the treatment of chronic pain.
Dr. Puig is currently a Research Assistant Professor in the Department of Anesthesia at the University of Pittsburgh. She continues her research in opioids in the context of pain and addition. She is working to understand the underlying mechanisms of opioids to find new ways to improve their safety and efficacy and hopes to become an independent investigator with her own laboratory soon.
Of the TRIUMPH Program, Dr. Puig notes "The course I took increased my knowledge on Human Pathophysiology and provided a better insight on how research can be more relevant to clinic. It also gave me the opportunity to meet some brilliant TRIUMPH
fellows and mentors. They are now part my professional network which is a very good asset for support and advice to my career."
Dr. Puig Publication History:
ORCID ID: 0000-0001-7200-1094
Deepavali Chakravarti, Ph.D.
Postdoctoral Fellow, Cancer Biology
MD Anderson Cancer Center
CPRIT TRIUMPH Fellow 2013-2016
CPRIT TRIUMPH Mentor: Ronald DePinho, Ph.D.
Dr. Chakravarti received a BS in Microbiology and an MS in Biotechnology from Bangalore University and earned a second MS in Biology from the University of Houston at Clear Lake. She received her PhD in Cancer Biology from The University of Texas MD Anderson and UTHealth Graduate School of Biomedical Sciences under the mentorship of Dr. Elsa Flores. Her graduate work focused on determining the role of p63 isoforms in the microRNA biogenesis pathway. She observed a global downregulation of all the mature microRNAs in the TAp63 null metastatic tumors that resulted in the identification of TAp63 as a transcriptional regulator of Dicer and MiR-130b. This work resulted in a co-first author manuscript in Nature in 2010. The ΔNp63 knock-out had epithelial developmental defects and died shortly after birth. Dr. Chakravarti found that the ΔNp63 isoform transcriptionally regulates DGCR8, which helps to maintain epithelial differentiation mainly through a panel of 7 microRNA signature. Loss of ΔNp63 or DGCR8 leads to the induction of multipotency in differentiated cells. This work resulted in a first author manuscript in PNAS in 2014. The TAp63-/- mice also exhibited an aging phenotype, and she performed experiments to determine whether this was due to the shortening of telomere length. The combined exposure to stem cells and telomere biology sparked her interest in pursuing research in this specific area. She recalls "I found it fascinating that telomeres could maintain stem cells and that shortening of telomeres can induce senescence in one context but induce genomic instability and cancer in another."
Joining the TRIUMPH Program shortly after earning her PhD, Dr. Chakravarti explored her interest in telomeres with Dr. Ronald DePinho, a world-renowned telomere and cancer biology expert. During her under Dr. DePinho’s mentorship, she has characterized the inflammatory bowel disease phenotype in telomere dysfunction mice (LSL-mTert;Lgr5CreERT2). She observed that these mice develop significantly high levels of inflammation in the large intestine, compared with the small intestine which is characterized mainly by apoptosis. She also found that reactivation of telomerase with the addition of tamoxifen, specifically in the Lgr5+compartment, is sufficient to suppress the inflammation in the intestine and regenerate the organ in 60% of animals, suggesting that inflammation is being driven by cell intrinsic factors. Given that one of the major differences between the large intestine and the small is microbial load, Dr. Chakravarti hypothesized that the colonic inflammatory phenotype could result from the interaction between cell intrinsic factors and the microbiome leading to hyper-activation of the immune system. RNA-seq revealed the inflammasome pathway to be one of the top pathways. Ultimately, she found that telomere dysfunction-mediated DNA damage can drive a ATM/cABL/Yap1 axis, which stabilizes and localizes Yap1 to the nucleus and can transcriptionally activate pro-IL-18(and other inflammasome genes) leading to the hyper-activation of the CD4+ T cell compartment culminating in an enhanced inflammatory response. Correlative data also demonstrated that this pathway active in the epithelia of biopsies from patients with inflammatory bowel disease.
Dr. Chakravarti notes "I have always been interested in pursuing translational research. The TRIUMPH program helped in orienting me towards patient-oriented research. Through the several courses in the program I had an opportunity to interact with patients undergoing treatments such as immunotherapy at MD Anderson, something that I feel is important for researchers like me to actually experience. I was struck by the impact that translational research like immunotherapy could actually have on patient treatment." She masterfully balances her high impact research with motherhood and enjoys spending time with her young daughter.
Amanda (Mandy) Haltom, Ph.D.
Postdoctoral Fellow, Department of Pediatrics
MD Anderson Cancer Center (Houston, TX)
CPRIT TRIUMPH Fellow 2015 - 2018
CPRIT TRIUMPH Mentor: Raghu Kalluri, M.D., Ph.D.
Dr. Haltom earned her Bachelor's of Science in Genetics from Texas A&M University, where she studied the role of the endosymbiont spiroplasma in the gut of Drosophila melanogaster and Drosophila hydei. She received her Ph.D. in Genes and Development from the MD Anderson UTHealth Graduate School of Biomedical Sciences (Houston, TX). Her dissertation work focused on elucidating the role of the post-translational modification O-glucose in the developing Drosophila photoreceptor.
Dr. Haltom joined the TRIUMPH Program in 2015 during her postdoctoral fellowship with Dr. Raghu Kalluri. Her research examined the effect of tumor growth on the biodistribution of normal tissue-derived exomes. Following her work in Dr. Kalluri's laboratory, she accepted a postdoctoral research fellowship in the Department of Pediatrics with Dr. Vidya Gopalakrishnan, where she studies the role of deubiquitinases in cerebellum development and medulloblastoma tumorigenesis. Dr. Haltom won the highly competitive 2017 American Association in Cancer Research Anna D. Barker Fellowship in Basic Cancer Research for her work in cancer research.
Dr. Haltom reflects "The TRIUMPH program really opened my eyes to translational research. The courses taught me how to apply my basic research knowledge to the patient bedside and what critical questions to ask."
Humberto Lara-Guerra, M.D., Ph.D., CCRP
Medical Director, Oncology
Aeglea Biotherapeutics (Austin, TX, USA)
CPRIT TRIUMPH Fellow 2010-2014
CPRIT TRIUMPH Mentor: Jack Roth, M.D., F.A.C.S.
Dr. Lara-Guerra received his Bachelor's of Science at Instituto Cultural Tampico (Tampico, Mexico) and his M.D. from the Universidad Autonoma de Tamaulipas. He then earned his M.Sc. from The University of British Columbia, where he studied the role of platelet activating factor in the mechanism of nitric oxide synthases after regional myocardial ischemia-reperfusion injury under the mentorship of Dr. Karim Qayumi and Dr. Richard Finley. During his time there, he was also part of the team that developed a surgical/radiological kit for the resection of pulmonary nodules. He continued his studies, earning his Ph.D. in the Clinical Investigator Stream at University of Toronto (Toronto, Ontario, Canada), where he created and lead a neoadjuvant clinical trials program focused in early lung cancer. He took this unique opportunity to publish the first worldwide trial on neoadjuvant EGFR TK inhibition previous to surgical resection. His laboratory work focused in a detailed evaluation of EGFR phosphorylation, mutation, and copy number in NSCLC, including before and after neo-adjuvant EGFR inhibition. Dr. Lara-Guerra joined the TRIUMPH program in 2010 under the mentorship of Dr. Jack Roth and examined exogenous restoration of TUSC2 expression in non-small cell lung cancer to overcome resistance to EGFR inhibition in a very translational research project, taking this gene therapy into clinical trials.
In his current position as Medical Director in Oncology at Aeglea Biotherapeutics, Dr. Lara-Guerra is responsible, from concept to implementation, for the clinical research efforts of the Oncology portfolio, currently focused on phase 1 and 2 trials of pegzilarginase, a pegylated arginase 1, as a monotherapy and in combination with anti-PD-L1 therapy. He functions as a Medical Monitor and creates and maintains a network of sites and key opinion leaders to efficiently run oncology-based trials to completion on time and with the highest data quality. He prepares study protocols, amendments, filing for investigational new drugs, prepares investigational medicinal product dossiers, and development safety update reports. Dr. Lara-Guerra presents projects at national and international meetings, prepares corresponding manuscripts, and brings leadership in translational research for effective biomarker development.
Dr. Lara-Guerra reflects "The TRIUMPH program was a unique experience that exposed me to sometimes opposite perspectives of drug development. On one hand, the coursework and the specific project under the mentorship of great academic leaders gave me the opportunity to lead an effort towards a clinical application. On the other, the clinical rotations, exposures, and interactions with physicians taught me to always think from the other side of the table and keep in mind the current problems that clinicians are confronting and also the practicality and essentiality of the solutions that we are developing."
Anne M. Bailey, Ph.D.
Clinical Genetics QA Scientist
QIAGEN Bioinformatics (Redwood City, CA, USA)
CPRIT TRIUMPH Fellow 2011-2013
CPRIT TRIUMPH Mentor: Garth Powis, Ph.D.
Dr. Bailey earned her B.S. in Organismal Biology from The University of Kansas and her Ph.D. in Toxicology from The University of Kansas Medical Center. Her Ph.D. dissertation focused on epigenetic regulation of farnesoid x receptor. Relocating to Houston, Dr. Bailey joined the TRIUMPH program in 2011 under the mentorship of Dr. Garth Powis. Here, she studied downregulation of farnesoid x receptor in colorectal cancer and screened novel cellular targets to exploit the unfolded protein response for the treatment of cancer.
Following her post-doctoral fellowship, Dr. Bailey joined the Institute for Personalized Cancer Therapy (IPCT) at MD Anderson as a Precision Oncology Scientist. During her nearly five years in this role, Dr. Bailey assisted in building an institutional pipeline for assessing tumor genomic profiles for personalized therapy options. She explains "The TRIUMPH program was a really great networking opportunity. I was able to write a phase I clinical trial, which introduced me to clinicians within the Institute for Personalized Cancer Therapy. I was then hired by IPCT as a scientist... This opportunity helped set me up on my current career trajectory."
Diane I. Scaduto, Ph.D.
Scientific Director & Founder
Laboratory Executive Management Leadership
alliantgroup (Houston, TX, USA)
CPRIT TRIUMPH Fellow 2011-2014
CPRIT TRIUMPH Mentor: Lynda Chin, M.D.
Dr. Scaduto completed her B.S. in Biochemistry and Microbiology at UCLA and her Ph.D. in Cell and Molecular Biology from Baylor College of Medicine in 2011, where her dissertation focused on molecular and biochemical characterization of genetic variants and their roles in human cancer. She joined the CPRIT TRIUMPH Postdoctoral Fellowship in Fall 2011 and worked under the mentorship of Dr. Lynda Chin to examine stromal-epithelial metabolic coupling in the melanoma tumor microenvironment.
Dr. Scaduto serves as Founder and Scientific Director for the Laboratory Executive Management Leadership Group in Houston, TX and works as a Scientific Consultant for alliantgroup in Houston. Previously, she served as Scientific Director for Applied Diagnostics, Inc. (Houston, TX) and Scientific Technical Lead for the Houston Forensic Science Center.
Jennifer Dennison, Ph.D.
Associate Director, Research Planning & Development
MD Anderson Cancer Center (Houston, TX, USA)
CPRIT TRIUMPH Fellow: 2009-2014
CPRIT TRIUMPH Mentor: Gordon Mills, M.D., Ph.D.
Dr. Dennison graduated summa cum laude with her B.S. in Chemical Engineering from Texas A&M University. After working in the pharmaceutical industry for a few years, she attended Indiana University, where she earned her Ph.D. in Pharmacology. Dr. Dennison's translational research project was conducted in the Division of Clinical Pharmacy. She hypothesized that expression of CYP3A5, an enzyme with common genetic polymorphisms, may be critical to the hepatic metabolism and ultimately the systemic exposure of vincristine during therapy. Unlike most basic science graduate projects, this project allowed her to collaborate with scientists from Eli Lilly and pediatric oncologists. First, she identified the major cytochrome P450 metabolite of vincristine and characterized its kinetics of biotransformation using recombinant enzymes, human liver microsomes, and cryopreserved hepatocytes. The major metabolite and parent drug were then quantified in plasma from ALL and rhabdomyosarcoma pediatric patients treated with vincristine at Riley Hospital (Indianapolis, IN) and the Children’s Memorial Hospital (Chicago, IL). After evaluating the in vitro findings and the data from these first clinical studies, the Children’s Oncology Group initiated more comprehensive clinical trials to determine whether CYP3A5 genetic polymorphisms were associated with vincristine drug clearance and clinical outcomes. Although the results are unknown at this time, it is anticipated that these trials may justify individualized therapy of vincristine for pediatric oncology patients.
After graduate school, to discover and evaluate new therapies in oncology, Dr. Dennison accepted a post-doctoral fellowship in the Varsha Gandhi laboratory at MD Anderson Cancer Center; this laboratory is proficient in cell culture and molecular biology techniques specific to hematological malignancies and nucleoside analogs. For her project, she evaluated the actions of a new class of nucleoside analogs, the 8-substituted adenosine analogs, using mantle cell lymphoma cell lines and primary cells. In addition, for the on-going phase I clinical trial of 8-chloro-adenosine (8-Cl-Ado) in chronic lymphocytic leukemia, Dr. Dennison determined the ex vivo response of the cells to 8-Cl-Ado and quantified the accumulation of active metabolites in primary cells. She expects that the results of her post-graduate studies will provide justification for future clinical trials of 8-substituted adenosine analogs in MCL and facilitate the understanding of 8-Cl-Ado intracellular metabolism in vivo. Dr. Dennison joined TRIUMPH Postdoctoral Research Fellowship Program and moved to the Department of Systems Biology. Her research here focused on metabolic heterogeneity in breast cancers. While the field of metabolism in oncology at the time almost exclusively focused on the Warburg effect, her research shows that cancers have differences in many key metabolic pathways that are associated with gene expression patterns, the molecular phenotype. Metabolic differences between cancers can be targeted and predict responses to current therapeutics. For example, Dr. Dennison recently evaluated a differentially expressed enzyme, lactate dehydrogenase B, which contributed to the glycolytic phenotype of basal breast cancers and predicted patient response to chemotherapy. She also identified histological markers of luminal breast cancers that contributed to heterogeneous protein expression and subtyping by reverse phase protein array.
Currently serving as the Associate Director for Research Planning and Development for the Red and Charline McCombs Institute for Early Detection and Cancer Treatment at MD Anderson, Dr. Dennison is responsible for the administrative and scientific leadership of the proteomics and metabolomics platform and clinical studies initiated by the McCombs Institute.
Dr. Dennison reflects "My experience in the TRIUMPH program allowed me to collaborate with clinicians and to understand how laboratory research can influence clinical practice. These experiences are essential to my current position within MD Anderson to lead teams that discover biomarkers for risk assessment and early detection of cancer. I still interact with many of the MD Anderson clinicians whom I met during my fellowship."
Nora Sanchez, Ph.D.
Precision Oncology Scientist
MD Anderson Cancer Center
TRIUMPH Postdoctoral Fellow: 2012-2015
TRIUMPH Program Mentor: Giulio Draetta, M.D., Ph.D.
Dr. Sanchez earned her B.S. in Cell and Molecular Biology from The University of Texas at Austin and her Ph.D. in Pharmacology from Vanderbilt University, where her Ph.D. thesis project focused on understanding the role of type III TGF-b receptor in coronary vessel development. During her time as TRIUMPH Postdoctoral Fellow, Dr. Sanchez led a translational research project to develop a platform for context-specific, functional genomic screens to identify and validate novel therapeutic targets in pancreatic cancer.
Dr. Sanchez joined the Institute for Personalized Cancer Therapy (IPCT) as a Precision Oncology Scientist in 2015 and plans, designs, and delivers requirements to software developers to support the creation and maintenance of informatics platforms to house Precision Oncology Decision Support knowledgebase. She manages collaborations between IPCT and Guardant Health to establish the utility of cfDNA testing in patients with advanced and/or non-biopsable cancers, and she contributes as a subject matter expert to MD Anderson Cancer Center's data governance committee on efforts to standardize and enhance the access and utility of clinical data.
Of the TRIUMPH program, Dr. Sanchez states "The overall diverse training received through TRIUMPH was instrumental to my current position. Specifically, exposure gained through clinical rotations through the various clinics helped develop a key understanding of the bottom line in patient care. Moreover, exposure to the regulatory aspects of clinical research was instrumental to understanding the challenges of moving science from bench to bedside."
Jodi McKenzie, Ph.D.
Clinical Research Scientist
Department of Investigational Cancer Therapeutics (Phase I Clinical Trials)
MD Anderson Cancer Center
TRIUMPH Postdoctoral Fellow: 2013-2016
TRIUMPH Mentor: Patrick Hwu, M.D.
Dr. McKenzie completed her B.A. in Biological Sciences from Mount Holyoke College, where she completed an honors thesis under Dr. Craig T. Woodward titled "The effect of beta-FTZ-F1 mutation on motor neuron structure and function in Drosophila melanogaster." She then earned her Ph.D. in Oncological Sciences from the University of Utah Huntsman Cancer Institute. Here, Dr. McKenzie examined the role of the inhibitor of apoptosis protein Survivin in melanoma cell motility and metastasis. She discovered that Survivin could enhance migration and invasion of melanoma cells through activation of the Akt pathway and upregulation of alpha-5-beta-1 integrin. During her TRIUMPH Postdoctoral Fellowship, she focused on improving melanoma patient response to cancer immunotherapy by developing novel combinations to improve response to T- cell based cancer immunotherapy. Using melanoma patient-derived cell lines and tumor infiltrating lymphocytes (TILs) and in vivo models, she was able to demonstrate that Topoisomerase I inhibitors (Top1) can improve the efficacy of T cell killing of tumor cells. This provided the basis for the development of a clinical trial concept looking at the combination of a Top1 inhibitor and a PD-1/-L1 immune checkpoint inhibitor.
In her current position as Clinical Research Scientist at MD Anderson Cancer Center, Dr. McKenzie works on developing clinical trials focused on combinations of immuno-oncology agents and DNA Damage Response-targeting agents.
Dr. McKenzie says this about our program: "The TRIUMPH program was very instrumental in helping me prepare for my career. Through the program I was able to learn more about human subject research and what’s involved in translating bench research into practical applications in the clinical setting."
PUBMED Author Link
Dong Yang, Ph.D.
Senior Research Scientist
Institute for Personalized Cancer Therapy
MD Anderson Cancer Center
TRIUMPH Postdoctoral Fellow: 2011 - 2015
TRIUMPH Mentors: Lynda Chin, M.D. and Khandan Keyomarsi, Ph.D.
Dr. Yang received his B.S. in Biochemistry and M.S. in Cell Biology from Beijing Normal University (Beijing, China). He completed his Ph.D. at Baylor College of Medicine in Biochemistry and Molecular Biology. His dissertation project focused on studying the function of telomere binding proteins and their role in dyskeratosis congenita. Dr. Yang joined the TRIUMPH program in 2011 and investigated targeted therapies for triple-negative breast cancer in preclinical models and utilized NGS to identify biomarkers for therapeutic response.
Following his post-doc, Dr. Yang joined Molecular Health Inc. and worked as a Clinical Science Liaison for two years before returning to his current position at MD Anderson. At the Institute for Personalized Cancer Therapy, Dr. Yang analyzes genomic data and provides personalized medical reports for cancer patients. In his time away from the laboratory, he enjoys playing and reading with his children.
He credits the TRIUMPH program with his career success explaining "The TRIUMPH program exposed me to the field of clinical research through the clinical rotations and curriculum related to clinical trial and human subject research. This program also tremendously helped me establish professional and personal connections, which led me to my current position. Before joining the TRIUMPH program, I viewed translational cancer research as a linear process from bench to bedside. Now, I realize that translational research should be a two-way road. The clinical feedback and data are as important as the figures generated in the lab. Without the TRIUMPH program, I would have never found my passion in clinical research and in the job I love."
PUBMED Author Link