Cancer Science & Therapy

Rachana Garg

Rachana Garg
University of Pennsylvania, School of Medicine, USA

Biography

My interest in cancer research started when I undertook a dissertation project during my undergraduate studies at the Division of Molecular Oncology, Institute of Cytology and Preventive Oncology (ICPO), under the guidance of Dr. B.C. Das (Founder Director of ICPO, India). This research was focused on dissecting the relationship between human papilloma virus and AP-1 transcription factor in the development of oral cancer. I had the opportunity to work with biopsy tissue specimens from patients with oral premalignant lesions. During this project, I learned numerous molecular biology techniques and inherently developed a strong penchant to pursue a research career in the oral cancer field. After qualifying through a competitive nationwide exam, I was awarded a prestigious five-year predoctoral fellowship from the CSIR foundation, India. As a CSIR research fellow, I joined ACTREC, a pioneering institute dedicated to cancer research in India. My Ph.D. research in Dr. Maru’s laboratory involved studying the chemopreventive role of dietary curcumin in regulating phase I/II enzymes in vivo via AhR and Nrf2 transcription factors. Moreover, I demonstrated that curcumin regulates phorbol ester-induced biochemical and molecular alterations in murine skin via protein kinase C. With the notion of identifying potential clinical biomarkers and to continue my research interest, I studied the effect of dietary turmeric at different stages of oral carcinogenesis in an experimental animal model. I observed that dietary turmeric modulates DMBAinduced p21, MAPKinases and transcription factors (AP-1 and NF-kB) to alter cellular responses related to inflammation, proliferation and apoptosis. In Dr. Maru’s lab, I acquired significant expertise in molecular carcinogenesis and chemoprevention and became highly proficient in the use of in vivo models, including DMBA-induced hamster buccal pouch model of oral cancer. My time in his lab was very productive, with my thesis work culminating with six publications, (four as first author: Garg et al. Carcinogenesis 2008; Garg et al. Carcinogenesis 2008b; Garg et al. Toxicol Appl Pharmacol 2008 and Garg et al. JEPTO 2009), a book chapter, and a review article. I am proud that my work led to several prizes and awards at national/international conferences. I then intended to extend my research to a challenging area: to explore the signaling networks underlying carcinogenesis with the purpose of providing a molecular basis for drug design. Therefore, I moved to the US to join Dr. Marcelo Kazanietz’s Laboratory at the University of Pennsylvania, as a postdoctoral fellow. Dr. Kazanietz is one of the prominent researchers in the field of PKC signaling and cancer. Initially, I started with an ongoing project in the laboratory wherein we observed that transgenic overexpression of PKCe in the mouse prostate induces preneoplastic lesions, and I was the co-author of a 2011 Cell Cycle paper reporting the results of the work. Our study was highlighted in the News and Views Section of Cell Cycle. Dr. Kazanietz then allowed me to design my own project in which I combined my doctoral expertise with the knowledge of PKC biology acquired in his laboratory and successfully demonstrated, through a mechanistic study, that PKCe facilitates the assembly of TNFR-I complex to regulate the NF-kB pathway in prostate cancer (Garg et al., JBC 2012). My thorough bioinformatics analysis to dissect the transcriptional networks controlled by PKC isozymes recently resulted in another first-authored publication (Garg et al, PLoS One 2013). Besides, I encapsulated our current understanding of PKCs in a recently published review article (Garg et al, Oncogene, 2013). I am currently working on two projects that are close to submission to major journals. In the first, by means of cellular and transgenic mice models, I demonstrated that COX-2, a well-known NF-kB regulated gene, acts as a potential mediator of PKCe oncogenesis in prostate cancer, a study that has been supported by a postdoctoral fellowship from the United States Department of Defense. As the PI of this DOD-sponsored grant, I gained experience in cellular, genetic, pharmacological and bioinformatics approaches to delineate signaling pathways that contribute to malignant transformation and developed skills working with xenograft and transgenic mice models. In the second, I identified cooperativity between PKCe and Pten loss for prostate cancer progression.

Research Interest

My research experiences have launched a long-term interest in understanding the indepth mechanisms underlying carcinogenesis, with the ultimate goal of identifying targets for drug-based therapies and developing strategies for overcoming treatment-related resistance observed in most prevalent cancer including prostate, lung and oral squamous cell carcinoma. As is evident from my educational background and trainings, my research experience spans over 10 years in the field of molecular carcinogenesis, cancer chemoprevention, cancer signaling and biochemistry. During undergraduate studies, I worked closely with oral cancer patients and detected and typed the HPV prevalence in the clinical samples. A short but an inspiring experience had made my career goal clearer and allowed me to stay focused in cancer biology field thus far. Moving ahead with my research interest, my doctoral work specifically focused on delineating the mechanism of turmeric/curcumin mediated chemoprevention in vivo model systems (liver, lung, skin and oral tissues of mice and hamsters) and to identify surrogate end point biomarkers for drug effect measurements. During my Ph.D. research, I thus gained thorough experience in working with in vivo cancer models, broadly targeting the carcinogenic process by employing chemopreventive compounds. To extensively explore the essential mechanisms in cancer development and to enhance my acquired skills in the cancer biology field, I joined the renowned signal transduction laboratory of Dr. Kazanietz at UPenn, with the main interest in protein kinase C (PKC). I have focused my postdoctoral studies largely on PKCe, a kinase that is upregulated in many epithelial cancers. Of note, the mechanism by which this kinase contributes to the initiation and maintenance of the prostate cancer phenotype is largely unknown and remains uninvestigated thus far. Using cellular, biochemical, and molecular profiling approaches, I characterized the signaling markers and molecular signature of the prostate lesions driven by PKC epsilon overexpression and Pten loss. I generated organ-specific models for transgenic expression of PKC isozymes and determined the phenotypical consequences of crossing these mice with other models harboring oncogenic alterations such as Pten and K-Ras relevant to prostate, oral and lung cancer. Furthermore, by intercrossing lung-specific mutant Ras mice (LSL-K-rasG12D) with PKCe KO mice, I demonstrated that deletion of the PKCe gene (PRKCE) in mice impaired Ras-mediated lung tumorigenesis. Using human prostate cancer clinical samples, my study established correlation of oncogenic PKC epsilon overexpression with other common alterations (Pten loss, NF-kB hyperactivation, COX-2 and CXCl13 up-regulation) in prostate cancer.

• Experienced in mammalian tissue culture, microarray and bioinformatics analysis, mouse biology, xenograft and transgenic mouse models.
• Excellent communication and organizational skills. Strong interpersonal skills. Ability to work independently and in matrix settings. • Skilled in scientific writings, grant applications and oral presentations
• Leadership/management and organizational role.

Specialties: Cancer biology, signal transduction, short and long term carcinogenesis study, tumor metastasis study, chemoprevention, transcriptional network analysis, microarray and bioinformatics analysis, drug target discovery, protein-protein interaction, DNA-protein interaction, in vivo and in vitro biology, establishing primary cell cultures from mouse prostate and lung tissues, migration, invasion, proliferation assays, gene silencing, generation of recombinant viruses and cell lines, analysis of scientific data, writing and editing.