Satya Narayan

Satya Narayan, PhD

Professor

Department: MD-ANATOMY-GENERAL
Business Phone: (352) 273-8163
Business Email: snarayan@ufl.edu

Teaching Profile

Courses Taught
2019-2024
GMS5057 Medical Cell Biology
2016-2023
GMS6001 Fundamentals of Biomedical Sciences I
2014-2017,2019-2023
GMS6647 Transcriptional and Translational Control of Cell Growth and Proliferation
2011-2012,2014-2021,2020-2023
DEN5121 Biochm Molec Cell Bio
2020-2024
GMS6691 Special Topics in Cell Biology and Anatomy
2012-2024
GMS6421 Cell Biology
2015-2016,2018-2021,2020-2024
GMS6009 Principles of Drug Action and Therapeutics
2009,2011-2013,2013-2016,2015-2024
GMS6064 Tumor Biology
2018
GMS7979 Advanced Research
2014,2016-2018
GMS6062 Protein Trafficking
2016
GMS6644 Apoptosis
2013-2014
GMS6692 Research Conference in Anatomy and Cell Biology

Research Profile

Targeting DNA repair and replication pathways for therapy of colorectal cancer: The traditional view of cancer development suggests that all neoplastic cells within a tumor contain tumorogenic growth capacity. However, it is evident from existing literature that only a small subset of bulk colon cancer cells (CRC-Cs) are able to initiate tumor growth. This sub-set of cancer-initiating cells is identified as colorectal cancer stem cells (CRC-SCs). CRC-SCs possess: (i) capacity for self-renewal, (ii) potential for multi-lineage differentiation, (iii) ability to drive continued expansion and survive into adverse tissue micro-environment, and (iv) ability to invade and metastasize. Elimination of the self-renewal capacity is required to overcome clinical relapses and ultimate death from CRC progression. Current standard therapy for CRC is based upon the DNA-damaging drug, oxaliplatin (OXR) and nucleotide analogue, 5-fluorouracil (5-FU). Although very common, metastatic colorectal cancer (CRC) remains one of the most challenging cancers to treat due to inherent drug resistance. This project will examine whether DNA repair and replication pathways can be targeted to enhance the cytotoxicity of CRC therapies. The overall goal of this pre-clinical study is to advance not only the understanding of DNA repair after standard CRC chemotherapy, but also to strategically develop novel small molecules that will be used to improve therapeutic outcomes for CRC patients. Our studies focus on both bulk and cancer stem cell populations as a target for therapeutic intervention of CRC. Our studies are also directed toward developing novel structure-based small molecule inhibitors for breast and pancreatic cancers and glioblastoma.

Mechanisms of cigarette smoke-induced breast and lung carcinogenesis: Many epidemiological studies suggest a strong link between smoking, the number of cigarettes smoked, and the incidence of breast cancer in women. However, other epidemiologic studies conflict with the association between cigarette smoking and breast cancer risk. In our studies by using an in vitro cell culture and in vivo animal models, we have shown that cigarette smoke condensate (CSC), a surrogate of cigarette smoke causes transformation of normal breast epithelial cells in the in vitro and in vivo studies. We have shown that adenomatous polyposis coli (APC) is a multifunctional protein having diverse cellular functions including cell migration, cell-cell adhesion, cell cycle control, chromosomal segregation and apoptosis plays a critical and new role in CSC-induced transformation of normal breast epithelial cells. We have examined the molecular mechanisms by which CSC and its major component, Benzo[α]pyrene, enhances APC-mediated accumulation of abasic DNA lesions, which is cytotoxic and mutagenic in nature, leading to enhanced neoplastic transformation of normal breast epithelial cells in an orthotopic xenograft model. Our current focus is to determine the molecular mechanisms by which DNA base excision repair might play a role in cigarette smoke-induced lung carcinogenesis.

Role of APC in DNA repair: Our recent studies suggest that the product of the adenomatous polyposis coli (APC) gene can modulate base excision repair (BER) pathway through an interaction with DNA polymerase β (Pol-β) and flap endonuclease 1 (Fen-1). Taken together with our finding that the transcription of APC is enhanced by alkylating agents, our results suggest that APC modulation of BER activity may play an important role in carcinogenesis and chemotherapy by determining whether cells with DNA damage survive or undergo apoptosis. These findings can have implications for the development of more effective strategies for chemoprevention, prognosis, and chemotherapy of colorectal as well as other types of solid tumors.

Open Researcher and Contributor ID (ORCID)

0000-0001-7080-8900

Publications

2024
Altering phosphorylation in cancer through PP2A modifiers.
Cancer cell international. 24(1) [DOI] 10.1186/s12935-023-03193-1. [PMID] 38184584.
2024
Molecular editing of NSC-666719 enabling discovery of benzodithiazinedioxide-guanidines as anticancer agents.
RSC medicinal chemistry. 15(3):937-962 [DOI] 10.1039/d3md00648d. [PMID] 38516586.
2023
EEPD1 promotes repair of oxidatively-stressed replication forks.
NAR cancer. 5(1) [DOI] 10.1093/narcan/zcac044. [PMID] 36683914.
2022
Sensitization of FOLFOX-resistant colorectal cancer cells via the modulation of a novel pathway involving protein phosphatase 2A
iScience. 25(7) [DOI] 10.1016/j.isci.2022.104518. [PMID] 35754740.
2022
Therapeutics Targeting p53-MDM2 Interaction to Induce Cancer Cell Death.
International journal of molecular sciences. 23(9) [DOI] 10.3390/ijms23095005. [PMID] 35563397.
2021
Molecular disruption of DNA polymerase β for platinum sensitisation and synthetic lethality in epithelial ovarian cancers.
Oncogene. 40(14):2496-2508 [DOI] 10.1038/s41388-021-01710-y. [PMID] 33674744.
2020
Clinical significance of a pvrl 4 encoded gene Nectin-4 in metastasis and angiogenesis for tumor relapse.
Journal of cancer research and clinical oncology. 146(1):245-259 [DOI] 10.1007/s00432-019-03055-2. [PMID] 31617074.
2020
The splicing component ISY1 regulates APE1 in base excision repair.
DNA repair. 86 [DOI] 10.1016/j.dnarep.2019.102769. [PMID] 31887540.
2019
A novel proteotoxic combination therapy for EGFR+ and HER2+ cancers.
Oncogene. 38(22):4264-4282 [DOI] 10.1038/s41388-019-0717-6. [PMID] 30718919.
2019
ASR352, A potent anticancer agent: Synthesis, preliminary SAR, and biological activities against colorectal cancer bulk, 5-fluorouracil/oxaliplatin resistant and stem cells.
European journal of medicinal chemistry. 161:456-467 [DOI] 10.1016/j.ejmech.2018.10.052. [PMID] 30384048.
2019
Nanoquinacrine sensitizes 5-FU-resistant cervical cancer stem-like cells by down-regulating Nectin-4 via ADAM-17 mediated NOTCH deregulation.
Cellular oncology (Dordrecht). 42(2):157-171 [DOI] 10.1007/s13402-018-0417-1. [PMID] 30603978.
2018
Design and synthesis of novel thiobarbituric acid derivatives targeting both wild-type and BRAF-mutated melanoma cells.
European journal of medicinal chemistry. 143:1919-1930 [DOI] 10.1016/j.ejmech.2017.11.006. [PMID] 29133035.
2017
NSC30049 inhibits Chk1 pathway in 5-FU-resistant CRC bulk and stem cell populations.
Oncotarget. 8(34):57246-57264 [DOI] 10.18632/oncotarget.19778. [PMID] 28915668.
2017
TRAIL enhances quinacrine-mediated apoptosis in breast cancer cells through induction of autophagy via modulation of p21 and DR5 interactions.
Cellular oncology (Dordrecht). 40(6):593-607 [DOI] 10.1007/s13402-017-0347-3. [PMID] 28936683.
2016
Interaction between APC and Fen1 during breast carcinogenesis.
DNA repair. 41:54-62 [DOI] 10.1016/j.dnarep.2016.04.003. [PMID] 27088617.
2015
Astroblastoma of cerebrum: A rare case report and review of literature.
Journal of cancer research and therapeutics. 11(3) [DOI] 10.4103/0973-1482.140800. [PMID] 26458709.
2015
Cyclin-Dependent Kinase Inhibitors as Anticancer Therapeutics.
Molecular pharmacology. 88(5):846-52 [DOI] 10.1124/mol.115.099325. [PMID] 26018905.
2015
Molecular mechanism of adenomatous polyposis coli-induced blockade of base excision repair pathway in colorectal carcinogenesis.
Life sciences. 139:145-52 [DOI] 10.1016/j.lfs.2015.08.019. [PMID] 26334567.
2015
NSC666715 and Its Analogs Inhibit Strand-Displacement Activity of DNA Polymerase β and Potentiate Temozolomide-Induced DNA Damage, Senescence and Apoptosis in Colorectal Cancer Cells.
PloS one. 10(5) [DOI] 10.1371/journal.pone.0123808. [PMID] 25933036.
2014
Anti-tumor activity of novel biisoquinoline derivatives against breast cancers.
Bioorganic & medicinal chemistry letters. 24(20):4850-3 [DOI] 10.1016/j.bmcl.2014.08.053. [PMID] 25240616.
2013
Adenomatous polyposis coli-mediated accumulation of abasic DNA lesions lead to cigarette smoke condensate-induced neoplastic transformation of normal breast epithelial cells.
Neoplasia (New York, N.Y.). 15(4):454-60 [PMID] 23555190.
2012
Adenomatous polyposis coli interacts with flap endonuclease 1 to block its nuclear entry and function.
Neoplasia (New York, N.Y.). 14(6):495-508 [PMID] 22787431.
2011
Assembly of the base excision repair complex on abasic DNA and role of adenomatous polyposis coli on its functional activity.
Biochemistry. 50(11):1901-9 [DOI] 10.1021/bi102000q. [PMID] 21261287.
2011
DNA polymerase β as a novel target for chemotherapeutic intervention of colorectal cancer.
PloS one. 6(2) [DOI] 10.1371/journal.pone.0016691. [PMID] 21311763.
2011
Polyphenol-rich sweet potato greens extract inhibits proliferation and induces apoptosis in prostate cancer cells in vitro and in vivo.
Carcinogenesis. 32(12):1872-80 [DOI] 10.1093/carcin/bgr215. [PMID] 21948980.
2010
Induction of reactive oxygen species-mediated autophagy by a novel microtubule-modulating agent.
The Journal of biological chemistry. 285(24):18737-48 [DOI] 10.1074/jbc.M109.091694. [PMID] 20404319.
2009
9-bromonoscapine-induced mitotic arrest of cigarette smoke condensate-transformed breast epithelial cells.
Journal of cellular biochemistry. 106(6):1146-56 [DOI] 10.1002/jcb.22099. [PMID] 19229861.
2009
A novel inhibitor of DNA polymerase beta enhances the ability of temozolomide to impair the growth of colon cancer cells.
Molecular cancer research : MCR. 7(12):1973-83 [DOI] 10.1158/1541-7786.MCR-09-0309. [PMID] 19996303.
2009
Amino acid Asp181 of 5′-flap endonuclease 1 is a useful target for chemotherapeutic development.
Biochemistry. 48(42):9952-8 [DOI] 10.1021/bi9010754. [PMID] 19769410.
2009
C/Ebp Beta-Mediated Transcriptional Regulation of Bcl-Xl Gene Expression in Human Breast Epithelial Cells in Response To Cigarette Smoke Condensate
Oncogene. 28(6):921-932 [DOI] 10.1038/onc.2008.429. [PMID] 19043455.
2009
Genome based cell population heterogeneity promotes tumorigenicity: the evolutionary mechanism of cancer.
Journal of cellular physiology. 219(2):288-300 [DOI] 10.1002/jcp.21663. [PMID] 19115235.
2008
A novel function of adenomatous polyposis coli (APC) in regulating DNA repair.
Cancer letters. 271(2):272-80 [DOI] 10.1016/j.canlet.2008.06.024. [PMID] 18662849.
2008
Discovery of a novel class of AKT pleckstrin homology domain inhibitors.
Molecular cancer therapeutics. 7(9):2621-32 [DOI] 10.1158/1535-7163.MCT-07-2276. [PMID] 18790745.
2007
Adenomatous polyposis coli-mediated hypersensitivity of mouse embryonic fibroblast cell lines to methylmethane sulfonate treatment: implication of base excision repair pathways.
Carcinogenesis. 28(10):2089-95 [PMID] 17522063.
2007
Estrogen-induced generation of reactive oxygen and nitrogen species, gene damage, and estrogen-dependent cancers.
Journal of toxicology and environmental health. Part B, Critical reviews. 10(4):235-57 [PMID] 17620201.
2007
Signature of mitochondria of steroidal hormones-dependent normal and cancer cells: potential molecular targets for cancer therapy.
Frontiers in bioscience : a journal and virtual library. 12:154-73 [PMID] 17127291.
2007
Structure/function analysis of the interaction of adenomatous polyposis coli with DNA polymerase beta and its implications for base excision repair.
Biochemistry. 46(49):13961-74 [PMID] 17999539.
2006
7,12-Dimethylbenzanthracene-dependent transcriptional regulation of adenomatous polyposis coli (APC) gene expression in normal breast epithelial cells is mediated by GC-box binding protein Sp3.
Carcinogenesis. 27(2):252-61 [PMID] 16150893.
2006
Mechanism of adenomatous polyposis coli (APC)-mediated blockage of long-patch base excision repair.
Biochemistry. 45(51):15903-14 [PMID] 17176113.
2005
Involvement of adenomatous polyposis coli in colorectal tumorigenesis.
Frontiers in bioscience : a journal and virtual library. 10:1118-34 [PMID] 15769611.
2005
Transforming growth factor -beta receptor signaling in cancer.
Frontiers in bioscience : a journal and virtual library. 10:1135-45 [PMID] 15769612.
2005
Tumor suppressor APC blocks DNA polymerase beta-dependent strand displacement synthesis during long patch but not short patch base excision repair and increases sensitivity to methylmethane sulfonate.
The Journal of biological chemistry. 280(8):6942-9 [PMID] 15548520.
2004
Cigarette smoke condensate-induced transformation of normal human breast epithelial cells in vitro.
Oncogene. 23(35):5880-9 [PMID] 15208684.
2004
Curcumin, a multi-functional chemopreventive agent, blocks growth of colon cancer cells by targeting beta-catenin-mediated transactivation and cell-cell adhesion pathways.
Journal of molecular histology. 35(3):301-7 [PMID] 15339049.
2004
Germline Telomere Length Dynamics and Mutagen Sensitivity Studies in a Family with Acute Reactions to Sun Exposure: Involvement of Three Generations.
Cancer genomics & proteomics. 1(3):199-208 [PMID] 31394654.
2004
N-methyl-N’-nitro-N-nitrosoguanidine-induced senescence-like growth arrest in colon cancer cells is associated with loss of adenomatous polyposis coli protein, microtubule organization, and telomeric DNA.
Molecular cancer. 3 [PMID] 14728717.
2004
Reduced levels of the adenomatous polyposis coli (APC) protein are associated with ceramide-induced apoptosis of colon cancer cells.
Journal of cancer research and clinical oncology. 130(12):695-703 [PMID] 15340841.
2004
Zinc stabilizes adenomatous polyposis coli (APC) protein levels and induces cell cycle arrest in colon cancer cells.
Journal of cellular biochemistry. 93(2):345-57 [PMID] 15368361.
2003
Carcinogenesis: The more we seek to know the more we need to know – Challenges in the post Genomic Era.
Journal of carcinogenesis. 2(1) [PMID] 12605710.
2003
Role of APC and DNA mismatch repair genes in the development of colorectal cancers.
Molecular cancer. 2 [PMID] 14672538.
2002
Beta-catenin-mediated transactivation and cell-cell adhesion pathways are important in curcumin (diferuylmethane)-induced growth arrest and apoptosis in colon cancer cells.
Oncogene. 21(55):8414-27 [PMID] 12466962.
2002
Long-patch base excision repair of apurinic/apyrimidinic site DNA is decreased in mouse embryonic fibroblast cell lines treated with plumbagin: involvement of cyclin-dependent kinase inhibitor p21Waf-1/Cip-1.
Oncogene. 21(38):5912-22 [PMID] 12185591.
2002
SN2 DNA-alkylating agent-induced phosphorylation of p53 and activation of p21 gene expression.
Mutation research. 500(1-2):17-30 [PMID] 11890931.

Grants

Apr 2023 ACTIVE
Novel therapeutic development for breast cancer
Role: Principal Investigator
Funding: FL DEPT OF HLTH BIOMED RES PGM/J&E KING
Jan 2015 ACTIVE
UF Health Cancer Center Bridge Seed Grant funded through the Florida Consortium of National Cancer Institute Centers Program
Role: Project Manager
Funding: UF HEALTH SHANDS HOSPITAL
Jan 2007 – Oct 2018
Consolidated UF Shands Cancer Center Research
Role: Project Manager
Funding: UF FOUNDATION

Education

Postdoctoral Fellow
1989-1991 · Department of Surgery, UTMB, Galveston, TX
Postdoctoral Fellow
1987-1989 · Institute for Environmental studies and Department of Biochemistry, Louisiana State University, Baton Rouge, LA
PhD, Biochemistry
1987 · Panjab University, Chandigarh, India
MSc, Biochemistry
1980 · University of Allahabad, India
BSc, Biology & Chemistry
1978 · University of Allahabad, India

Contact Details

Phones:
Business:
(352) 273-8163
Emails:
Business:
snarayan@ufl.edu
Addresses:
Business Mailing:
PO Box 100235
GAINESVILLE FL 32610
Business Street:
ARB R4-224
1200 Newell Drive
GAINESVILLE FL 32610