Subbarayalu, PanneerdossGraduate School of Biomedical Sciences |
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| Year | Degree | Discipline | Institution |
| 2011 | Postdoctoral Training | MicroRNA | University of Texas Health Science Center at San Antonio San Antonio , TX |
| 2008 | Postdoctoral Fellowship | Lung Cancer & Reproductive Biology | University of Virginia Charlottesville , VA |
| 2005 | Postdoctoral Fellowship | Reproductive Biology | Center for Cellular and Molecular Biology (CCMB) Hyderabad , India |
| 2004 | PhD | Science/Zoology (Reproductive Physiology) | University of Rajasthan Jaipur , India |
| 1999 | MS | Zoology | Pondicherry University Puducherry , India |
| 1997 | BS | Zoology | University of Madras Chennai , India |
Cancer Biomarker- Cancer Testis Antigen CABYR- Diagnostic Biomarker for Lung Cancer: Splice variants and protein isoforms of the cancer-testis neoantigen CABYR were studied in primary tumors of non-small cell lung cancer [NSCLC] and derived cell lines. Incidences of CABYR transcripts in 16 NSCLC biopsies studied by RT-PCR were 56% for isoform 1, 88% for isoforms 3 and 5 combined, 75% for isoform 5, and 69% for isoform 6. A previously unreported CABYR isoform, utilizing splice junctions MYR-VEK and QML-AMA, was identified by PCR in 88% of NSCLC tissues and was designated isoform 8. NSCLC showed no evidence of CABYR isoform 2 or 4 transcripts. All lung squamous cell carcinomas (n=9) and 71% of adenocarcinomas (n=7) expressed CABYR isoform 3 transcripts. NSCLC cell lines NCI-H226 (squamous) and A549 (adenocarcinoma) showed CABYR transcripts encoding isoforms 1, 3, 5, 6 and 8. Transfection of various CABYR splice variants into HEK293 cells revealed translation of multiple CABYR proteins indicating use of internal start sites. Western blots of NSCLC tumor extracts revealed CABYR isoforms, especially the 50 kDa (isoform 1) and 27 kDa coding region B-containing proteins. Immuno-histochemical analysis of a tumor microarray using the 3A4 mAb to CABYR isoforms I and II showed 43% of NSCLC specimens were positive at a 1:1000 dilution. Due to its post-meiotic expression in the normal testis CABYR possesses characteristics of a biomarker and/or therapeutic neoantigen particularly in lung squamous cell carcinomas. mAb 3A4 represents a useful probe for detecting CABYR extracted from NSCLC in immunochemical assays. The complementarity determining regions of this mAb represent candidate domains for CABYR-directed immunotheranostics (Panneerdoss et al., 2018 Oncotarget under Revision). |
MicroRNA in Cancer- microRNAs as novel a therapeutic targets to treat drug-resistant breast cancers. Breast cancer is the second leading cause of cancer-related deaths in the United States. Chemotherapy is routinely used to treat breast cancer patients. However, many patients develop drug resistance and don?t respond to chemotherapy drugs leading to their shorter survival. Even, patients who do respond have severely compromised quality of life due to debilitating side effects associated with these drugs. Our long-term objective is to discover novel therapeutic targets that could enhance efficacy of current chemotherapeutics and prolong survival of breast cancer patients. Towards this goal, recently, in a large genomic screening study, we discovered that small non-coding RNAs, miRNAs, may mediate drug sensitivity/resistance in breast cancer. We are currently using tumor xenograft and human tumor explant models to characterize the function of sensitizer miRNA. |
MicroRNA in Testis- In addition to the role of miRNAs in cancer biology, we are also actively engaged in understanding the role of androgen responsive miRNA in Sertoli cells (Panneerdoss et al., 2012). How androgen regulates spermatogenesis is still unresolved. Here, we show that androgen controls key spermatogenic events by regulating microRNAs and their targets in the testis. In particular, we find that androgen-responsive miR-471 expression coincides with emergence of androgen action within Sertoli cells and male germ cell development. Transgenic mice overexpressing miR-471 demonstrated increased germ cell apoptosis, defective germ cell meiotic progression, impaired spermatid differentiation, compromised Sertoli cell-Sertoli cell adhesion at the blood-testis barrier resulting in severely reduced fertility. Importantly, our analysis revealed that miR-471 regulates Sertoli cell phagocytosis of apoptotic germ cells in an androgen-dependent manner. miR-471 transgenic mice represent a unique genetic model for studying the function of androgen-regulated events in Sertoli ? germ cell communication including phagocytosis and maintenance of optimal male fertility. |
RNA Methylation and Breast Cancer- We are also interested in understanding RNA methylation pattern in breast cancer.Unlike DNA methylation, little is known about the epigenetic modifications to mRNAs and their role in tumorigenesis. We recently found that RNA N6-adenosine methyltransferase protein METTL14 supports breast cancer growth and progression. METTL14 knockdown inhibited the long-term survival, migration as well as invasion of breast cancer cells. In addition, METTL14 silencing suppressed tumor growth in the breast tumor xenograft model. Importantly, we showed that METTL14 mediated its pro-tumorigenic role by activating the expression of RNA binding protein HuR and consequently inducing the transcriptional stability of TGFβ and its signaling partners cyclin D1 and smad3. Our results revealed that m6A RNA methylation levels of TGFβ, cyclin D1 and smad3 were significantly lower in breast cancer patients compared to normal matched controls. Interestingly, we found that METTL14 levels strongly correlated with the poor survival of the breast cancer patients. Taken together, these findings suggest that METTL14 and mRNA methylation may play a vital role in breast cancer growth and progression through post-transcriptional regulation of key pro-tumorigenic genes (Panneerdoss et al., 2018; Science Advances Under Review). We are extending our investigation towards RNA methylation role in testicular germ cell tumor. |
RNA binding protein role in Tumor Biology- MATRIN 3: A Novel Microtubule Associated RNA Binding Protein that Acts as a Potent Tumor Suppressor. Microtubules are highly dynamic components of the cytoskeleton that plays an important role in a wide range of cellular processes including cell division, cell motility and intracellular transport. Increasing evidence suggests that alterations in microtubule dynamics is critical for cancer growth and metastasis. The microtubule associated proteins (MAPs) are one group of proteins that regulate microtubule dynamics and, therefore, can affect sensitivity of cancer cells to microtubule targeting drugs. We discovered a novel microtubule associated protein ?Matrin 3 (MATR3)? that is known to bind to RNA and play a critical role in RNA transport and RNA stabilization. Immunofluorescence analysis revealed that that though MATR3 is predominantly a nuclear protein, it translocates to cytoplasm and interacts with microtubule when breast cancer cells are treated with microtubule stabilizer chemotherapy drug paclitaxel. Interestingly, our results reveal that MATR3 acts as a potent tumor suppressor as it inhibits colony formation, migration and invasion of breast cancer cells in addition to suppressing breast tumor growth in vivo. Analysis of breast cancer samples showed a significantly decreased expression of MATR3 when compared to normal adjacent tissues. Experiments are underway to understand that how MATR3 may affect microtubule dynamics and the mechanism by which MATR3 imparts its tumor suppressor function. |
Sperm Maturation and In vitro Fertilization (IVF)- Sperm undergoes a maturational process called capacitation in the female reproductive tract, which makes them fertilization-competent. The hallmarks of capacitation are protein tyrosine phosphorylation, hyperactivation and acrosome reaction. Dihydrolipoamide dehydrogenase (DLD) is a post-pyruvate metabolic enzyme and is tyrosine phosphorylated during sperm capacitation. We determined the role of DLD in post-capacitation events of fertilization and embryo development. DLD inhibition in sperm led to defective fertilization, where the release of the second polar body and formation of pronuclei were not seen (a condition similar to Digyny). Analysis of these sperm revealed that unlike in control sperm, intracellular pH (pHi) did not increase in DLD inhibited sperm during capacitation. Thus, increases in sperm intracellular pH is a pre-requisite for successful fertilization and DLD is required for the capacitation-dependent increase in intracellular pH of sperm |
| Date | Description | Institution | # Students |
| 8/2013 - Present | Masters' Thesis Directed | GCCRI, UTHSCSA | |
Journal Article |
| Onyeagucha BC, Panneerdoss Subbarayalu, Abdelfattah N, Rajamanickam S, Timilsina S, Guzman RM, Zeballos C, Eedunuri V, Bansal S, Mohammad TA , Chen Y, Vadlamudi R, Rao MK. Novel post-transcriptional and post-translational regulation of proapoptotic protein BOK and anti-apoptotic protein Mcl-1 determine the fate of breast cancer cells to survive or die Oncotarget 2017 Sep;8:85984-85996. |
| Rajamanickam S, Panneerdoss S, Gorthi A, Timilsina S, Onyeagucha B, Kovalsky D, Hanes MA, Vadlamudi R, Chen Y, Bishop AJ, Arbiser JL, Rao MK. Imipramine Blue - A Potent Therapeutic Regimen that Suppresses Breast Cancer Growth and Metastasis by inhibiting DNA repair Clinical Cancer Research 2016 Jul;22(14):3524-3536. |
| Heping Zheng, Arabinda Mandal, Igor A. Shumilin, Mahendra D. Chordia, Subbarayalu Panneerdoss, John C. Herr, and Wladek Minor. Sperm Lysozyme-Like Protein 1 (SLLP1), an intra-acrosomal oolemmal-binding sperm protein, reveals filamentous organization in protein crystal form Andrology 2015 Jul;3(4):756-771. |
| Suryavathi V*, Panneerdoss S*, Wolkowicz MJ, Shetty J, Sherman NE, Flickinger CJ, Herr JC. *Equal First Author. Dynamic Changes in Equatorial Segment Protein 1 (ESP1) N and O-Glycosylation during Mouse Spermiogenesis Biology of reproduction 2015 May;92(5):1-16. |
| Rao MK, Matsumoto Y, Richardson ME, Panneerdoss S, Bhardwaj A, Ward JM, Shanker S, Bettegowda A, Wilkinson MF. Hormone-induced and DNA Demethylation-induced Relief of a Tissue-specific and Developmentally Regulated Block in Transcriptional Elongation J Biol Chem 2014 Dec;289(5):35087-35101. |
| Siva AB*, Panneerdoss S*, Sailasree P, Singh DK, Kameshwari DB, Shivaji S. *Equal First Author. Inhibiting sperm pyruvate dehydrogenase complex and its E3 subunit, dihydrolipoamide dehydrogenase affects fertilization in Syrian hamsters PLoS One 2014 May;9(5). |