Annie Fuller, CBGN PhD Student, 2021, 2022 T32 Fellow
T32 mentor and Thesis advisor: Dr. Kelly Whelan, Assistant Professor at the Fels Cancer Institute for Personalized Medicine
“I began my research experience in the lab of Dr. Robert Barnet my freshman year at The College of William & Mary, where I examined light-enhanced anxiety and context-conditioned fear via startle and freeze responses in rats following chronic nicotine exposure. After two years, I earned a position as lab manager and trained students on experimental protocols. Concurrently, I explored public health through ethnographic data collection on first-generation African immigrant experiences with U.S. healthcare under the guidance of Dr. Mei-Mei Sanford. This research culminated in a senior honors thesis, for which I was awarded highest honors. I also worked in the lab of Dr. Matthew Wawersik during my senior year to annotate the genome of Drosophila takahashii and identify regulators of the testis stem cell niche through RNAi analysis. I continued to gain valuable laboratory experience as a postbaccalaureate fellow at the National Institutes of Health, where I characterized murine retinal ganglion cells via transcription factor expression. During my fellowship, I presented my work at the Society for Neuroscience 2019 annual meeting and submitted a co-first author publication to Journal of Comparative Neurology in 2020. My dedication to biomedical research remained strong as I explored the fields of neuroscience, public health, and genetics – upon completing my first year of graduate school at Temple University Lewis Katz School of Medicine, cancer and genome biology have emerged as a passionate focus within this dedication. Accordingly, I have joined the lab of Dr. Kelly Whelan. Her expertise in disease pathobiology and cell biology will greatly benefit me as I enter this field of study, and her commitment to diversity and mentorship align well with my values. My thesis work will define the epithelial landscape in esophageal squamous cell carcinoma, providing me with the opportunity to develop technical skills and conceptual expertise in the field of cancer biology. I will take full advantage of the excellent resources available in the T32 program, LKSOM, and the Whelan lab in order to establish a solid foundation for my professional development as a future independent investigator.”
Publications
Parmhans N*, Fuller AD*, Nguyen E, et al. Identification of retinal ganglion cell types and brain nuclei expressing the transcription factor Brn3c/Pou4f3 using a Cre recombinase knock-in allele. J Comp Neurol. 2021; 529: 1926– 1953. https://doi-org.libproxy.temple.edu/10.1002/cne.25065. (PMID 33135183) *Equal contribution
Jorge Canar CBGN PhD Student, 2021, 2022 T32 Fellow
T32 mentor and Thesis advisor: Dr. Ana Gamero, Associate Professor at the Department of Medical Genetics and Molecular Biochemistry
“I’m a PhD student in the BMSC Program at LKSOM at Temple University. With my parents’ support, I’m proud to be first in my family to graduate from college and very committed to pursuing a higher-level education. As a Hispanic/Latino born in the US and as an underrepresented minority (URM) student in the biomedical sciences, I’m aware of the challenges ahead of me. Even so, I’m very enthusiastic about the prospect of becoming an independent scientist to teach and mentor the next generation of young minds. My interest in science and, particularly in cancer research, developed as an undergraduate student at Hunter College. I joined Dr. Jill Bargonetti’s lab, where I conducted studies on C. elegans p53 (CEP-1). I also contributed to a project on mutant p53 in triple negative breast cancer that led to my first publication. My love for science and hard work under the guidance of Dr. Bargonetti led to awards as an undergraduate researcher. I learned from this experience that being in a learning environment with the right mentor that matches my scientific goals is key to success.
After completing my first year in the graduate program, I selected Dr. Gamero as my PhD advisor. I selected a project to characterize mutations in the transcription factor STAT2 that are found in tumors for hallmarks of tumorigenicity and response to interferons. I find this project exciting as it will let me acquire new knowledge and learn how to work with animal models of cancer, apply molecular and cellular biology and genetics approaches to test data-driven hypothesis. I’m confident that under Dr. Gamero’s mentorship and the opportunities provided by the T32 program I will strengthen my scientific knowledge and presentation skills to communicate my findings and generate preliminary data to apply for predoctoral fellowships. Being a recipient of a T32 grant offers me the opportunity to immerse in the field of cancer biology and signal transduction. I strongly believe that my choice of mentor, the nature of the project, and the training provided will give me a first step towards my long-term goal in teaching and research.”
Publications
Xiao, G., Lundine, D., Annor, G. K., Canar, J., Ellison, V., Polotskaia, A., Donabedian, P. L., Reiner, T., Khramtsova, G. F., Olopade, O. I., Mazo, A., & Bargonetti, J. (2020). Gain-of-Function Mutant p53 R273H Interacts with Replicating DNA and PARP1 in Breast Cancer. Cancer Research, 80(3), 394–405
Xinpei Jiang, CBGN PhD Student, 2022 T32 Fellow
T32 mentor and Thesis advisor: Dr. Israel Cañadas, Assistant Professor at the Fox Chase Cancer Center Department of Blood Cell Development and Function
“I am an immigrant, and the first in the family to attend a university and a graduate school. I started my science training at University of Pennsylvania, where I received my B.A. in Molecular Biology. My passion for biomedical science is caused by my desire to improve the lives of others medically, and I want to use biological science findings in creating new therapies for diseases. What further confirmed my decision to pursue a career in a Biomedical Research Institution making novel discoveries was my research experience at the laboratory of Dr. Shuxin Li at the Lewis Katz School of Medicine (LKSOM) at Temple University. While at LKSOM, I helped to develop combinatorial therapeutics to promote nerve regeneration using Adeno-associated virus gene therapy methodologies. I firmly believe that translational research can bring cures and high-quality treatments to improve patients’ health. My previous journeys not only helped me gain a sense of purpose, more importantly, the stamina to overcome many challenges ahead to make the impossible possible.
During my first PhD rotation at the laboratory of Dr. Israel Cañadas, I was puzzled by tumor heterogeneity, and it transformed my understanding of tumor progression. My current graduate work at Fox Chase Cancer Center (FCCC) is under the mentorship of Dr. Israel Cañadas and my research interests are focused on targeting innate immunity in Small Cell Lung Cancer with a goal to discover novel therapeutic targets that can restore immunogenicity and overcome tumor resistance to immunotherapy. I am excited about the translational impact of my PhD studies at LKSOM / FCCC. I firmly believe that my PhD training will benefit very significantly from the unique and dynamic training activities provided by the T32 program, LSOM, FCCC, and Cañadas lab beyond those offered by the Biomedical Science Graduate Program. This predoctoral T32 fellowship not only will allow me to become a rounded independent thinker, but one step closer to reach my ambitious goal of becoming an independent researcher."
Publications
Bernstein DL, Jiang X, Rom S. let-7 microRNAs: Their Role in Cerebral and Cardiovascular Diseases, Inflammation, Cancer, and Their Regulation. Biomedicines. 2021 May 26;9(6). doi: 10.3390/biomedicines9060606. Review. PMID: 34073513; PMCID: PMC8227213.
Nathan FM, Ohtake Y, Wang S, Jiang X, Sami A, Guo H, Zhou FQ, Li S. Upregulating Lin28a Promotes Axon Regeneration in Adult Mice with Optic Nerve and Spinal Cord Injury. Mol Ther. 2020 Aug 5;28(8):1902-1917. doi: 10.1016/j.ymthe.2020.04.010. Epub 2020 Apr 15. PMID: 32353321; PMCID: PMC7403348.
Ohtake Y, Sami A, Jiang X, Horiuchi M, Slattery K, Ma L, Smith GM, Selzer ME, Muramatsu SI, Li S. Promoting Axon Regeneration in Adult CNS by Targeting Liver Kinase B1. Mol Ther. 2019 Jan 2;27(1):102-117. doi: 10.1016/j.ymthe.2018.10.019. Epub 2018 Nov 1. PMID: 30509565; PMCID: PMC6319317.
David Glass, CBGN PhD Student, 2022 T32 Fellow
T32 mentor and Thesis advisor: Dr. Neil Johnson, Associate Professor at the Fox Chase Cancer Center, Molecular Therapeutics Program
"I started my training at Brandeis University where I earned my B.S. in biochemistry, biology, and chemistry. While at Brandeis, I began undergraduate research in Dr. Susan Lovett’s laboratory which studies mechanisms of DNA repair, recombination, and mutagenesis in E. coli and S. cerevisiae. After graduation, I continued my research with Dr. Lovett as a research technician, a position which resulted in co-authorship on four peer reviewed publications. Projects I worked on with Dr. Lovett included uncovering the roles of E. coli RadD and Uup proteins in processing post-replication single strand DNA gaps, assessing the DNA damage/repair pathways induced by DNA-protein crosslinks in E. coli, and examining the functions and interactions of E. coli replication proteins HolC and HolD with DNA-damage inducible helicase YoaA.
I ultimately decided to join the Biomedical Sciences Ph.D. program at the Lewis Katz School of Medicine because I wanted my research to have an impactful translational component in addition to the basic science aspects of the research. During my first-year lab rotations, I rotated with Dr. Neil Johnson, an internationally recognized leader in the DNA repair field, at Fox Chase Cancer Center, and was immediately interested in his research. Dr. Johnson’s lab works on DNA damage response mechanisms that promote resistance to chemotherapies, with a particular focus on BRCA1 mutant breast and ovarian cancers. Joining Dr. Johnson’s lab for my Ph.D. work was a natural progression since it combines the DNA repair and molecular biology components I enjoyed at Brandeis with an added translational facet. My thesis project will revolve around Polymerase theta, a critical component of theta-mediated end joining (TMEJ) which is an essential backup DNA repair pathway to homologous recombination (HR). Since Polymerase theta is essential to TMEJ, it is synthetic lethal in HR deficient settings, making it an attractive therapeutic target for HR deficient cancers (like BRCA1 mutant cancers). Currently, Polymerase theta inhibitors are in preclinical development and are beginning to enter clinical trials, making questions surrounding Polymerase theta even more pressing. I look forward to taking full advantage of all the T32 program has to offer, as I’m confident it will improve and expand my thinking as a scientist, offer opportunities to practice presenting and effectively communicating data, and expose me to the exciting projects being conducted by peers."
Publications:
Klaric JA, Glass DJ, Perr EL, Reuven AD, Towne MJ, Lovett ST. 2021. DNA damage-signaling, homologous recombination and genetic mutation induced by 5-azacytidine and DNA-protein crosslinks in Escherichia coli. Mutat Res. 822(111742):111742. doi: 10.1016/j.mrfmmm.2021.111742. http://dx.doi.org/10.1016/j.mrfmmm.2021.11174
Sutera VA, Weeks SJ, Dudenhausen EE, Baggett HBR, Shaw MC, Brand KA, Glass DJ, Bloom LB, Lovett ST. 2021. Alternative complexes formed by the Escherichia coli clamp loader accessory protein HolC (x) with replication protein HolD (ψ) and repair protein YoaA. DNA Repair (Amst). 100(103006):103006. doi:10.1016/j.dnarep.2020.103006. http://dx.doi.org/10.1016/j.dnarep.2020.103006.
Sutera VA, Sass TH, Leonard SE, Wu L, Glass DJ, Giordano GG, Zur Y, Lovett ST. 2021. Genetic analysis of DinG family helicase YoaA and its interaction with replication clamp loader protein HolC in Escherichia coli. J Bacteriol. 203(18):e0022821. doi:10.1128/JB.00228-21. http://dx.doi.org/10.1128/JB.00228-21.
Romero ZJ, Armstrong TJ, Henrikus SS, Chen SH, Glass DJ, Ferrazzoli AE, Wood EA, Chitteni-Pattu S, van Oijen AM, Lovett ST, et al. 2020. Frequent template switching in postreplication gaps: suppression of deleterious consequences by the Escherichia coli Uup and RadD proteins. Nucleic Acids Res. 48(1):212–230. doi:10.1093/nar/gkz960. http://dx.doi.org/10.1093/nar/gkz960.
Daniel Kantner, MCBS PhD Student, 2022 T32 Fellow
T32 mentor and Thesis advisor: Dr. Nathaniel Snyder, Associate Professor Associate Professor at the Department of Cardiovascular Sciences
"Throughout my early life, I had always marveled at how a single alteration of a single biological molecule could result in the development of some diseases. This fascination, along with my general interest in scientific disciplines, spurred me to obtain an undergraduate degree in biochemistry from Albright College. From there, I took a circuitous route to graduate school. I worked for over five years as an analytical chemist, during which time I had the opportunity both to use technically advanced and highly quantitative instrumentation to analyze pharmaceuticals and also to interact with client representatives involved in early-phase pharmaceutical research projects. During that time, I realized that my interests and skills would be well suited for bioanalytical research, so I pursued a master’s degree from Drexel University. Under the tutelage of Dr. Joris Beld, I characterized bacterial cobamide amidohydrolases using liquid chromatography-mass spectrometry (LC-MS) and was exposed to the broad spectrum of possible applications of LC-MS in biological research. My time at Drexel University only strengthened my desire to pursue a path related to bioanalytical techniques as they apply to biochemistry.
At Temple, I will be examining the complex interplay between metabolism, signaling, and epigenetics, which has relevance to both fundamental biology/biochemistry and metabolic diseases. My current project in the lab of Dr. Nathaniel Snyder involves interrogating metabolite control of epigenetics via subcellular metabolism and modification of histones. This line of research is a perfect illustration of the interface of biochemistry and cutting-edge bioanalytical techniques. The support, resources, and training provided by the T32 program will be conducive not only to my interest in using cutting-edge analytical techniques to bridge biological disciplines but also to my career goal of attaining an advanced position within the pharmaceutical or biotechnical industry."
Benjamin Ferman, CBGN PhD Student, 2022 T32 Fellow
T32 mentor and Thesis advisor: Dr. Johnathan R. Whetstine, Professor at the Fox Chase Cancer Center, Director of the Cancer Epigenetics Institute and Leader of the Cancer Signaling and Epigenetics Program
"Like so many people, cancer stole a cherished relative at an early age and deprived me of a relationship I always wished I could have. This loss led me to study bioengineering with the hope of one day working in cancer research. After graduating from Lehigh University, I joined Dr. Fiona Simpkins’ Lab at the University of Pennsylvania. The goal of my projects in the lab was to identify novel targets and strategies to overcome resistance in ovarian cancers by exploiting genetic vulnerabilities, in order to optimize synthetically lethal therapeutic approaches. One of our key findings was that low-dose WEE1 inhibition and ataxia telangiectasia and Rad3-related (ATR) inhibition (WEE1i-ATRi) synergistically decreases viability and colony formation and increases replication fork collapse and double-strand breaks in a CCNE1 copy number dependent manner in ovarian tumor models. My studies demonstrated that CCNE1 copy number is a clinically relevant biomarker predicting responsiveness for specific subsets of ovarian and endometrial cancer to WEE1i + ATRi. My co-author work on this project was published in Cell Reports Medicine in 2021.
My interest in mechanistically studying replication mis-regulation and oncogenic amplifications led me to Dr. Johnathan Whetstine’s laboratory at the Fox Chase Cancer Center, through my Ph.D. program at Temple University School of Medicine. Dr. Whetstine is a world leader in chromatin biology and extrachromosomal DNA (ecDNA). As a Ph.D. student in Dr. Whetstine’s laboratory and with the opportunities provided by the T32 program, I have unrivaled mentorship and countless resources available to me so that I can pursue my scientific interests. In Dr. Whetstine’s laboratory, my research interests center on understanding how modulation of our epigenome can affect replication timing (RT) and its association with genome architecture and amplification, especially in cancer. Our lab previously established how chromatin modifications can drive both DNA amplifications and alter replication timing through the regulation of the replication machinery. Using the resources available to me though Dr. Whetstine, the T32 program and Fox Chase Cancer Center, my thesis is focused on elucidating the effects of chromatin modifications on RT and how these changes impact DNA amplification. These studies will hopefully provide me the foundation for my career as an independent investigator."
Publications
Xu H, George E, Kinose Y, Kim H, Shah JB, Peake JD, Ferman B, Medvedev S, Murtha T, Barger CJ, Devins KM, D'Andrea K, Wubbenhorst B, Schwartz LE, Hwang WT, Mills GB, Nathanson KL, Karpf AR, Drapkin R, Brown EJ, Simpkins F. CCNE1 copy number is a biomarker for response to combination WEE1-ATR inhibition in ovarian and endometrial cancer models. Cell Rep Med. 2021 Sep 23;2(9):100394. doi: 10.1016/j.xcrm.2021.100394. PMID: 34622231; PMCID: PMC8484689.