Sanjay Premi, PhD

Dr. Premi’s research program focuses designing unique, therapeutic, and preventive approaches against skin cancers. We combine pure cancer biology with the next generation chemical approaches to identify novel targets and pathways responsible for progression and therapeutic resistance in melanoma.

Associations

• Tumor Microenvironment and Metastasis
• Cutaneous Oncology
• Molecular Medicine Program
• Melanoma & Skin Cancer Center of Excellence

Education & Training

Graduate:

• National Institute of Immunology, PhD - Human Molecular Genetics
• Jawaharial Nehru University, MS - Biotechnology

Dr. Premi’s lab focusses on designing novel, preventive and therapeutic strategies against skin cancers, including melanoma.  Currently, there are three main interests of the lab. First is identifying novel therapeutic targets for melanoma and other skin cancers. We are interested in investigating the role of nitric oxide and its metabolites in de-sensitizing the melanomas to current therapeutic modalities. In particular, we focus on the role of nitrosylation and nitration, two posttranslational modifications induced by nitric oxide, in hyperactivating the RAS-MEK-ERK cascade, and also in deactivating antimelanoma immunity. We aim at identifying nitrosylation and nitration driven mechanisms of melanoma progression which will provide potential targets for novel therapeutic approaches against melanoma. Second major focus of the Premi lab is investigating the carcinogenicity of skin pigments. Contrary to their sun-protective role, we discovered that melanin-oxidation by nitric oxide synthase, produces carcinogenic, melanin-carbonyls (MCs). We are investigating the role of melanin-carbonyls in dysregulating melanocytic physiology and promoting melanoma progression and therapy resistance.  Central goal of this research focus is to identify MC-mediated, non-classical regulation of melanoma progression and therapy resistance that could be used as a novel vulnerability against melanoma. The third major research focus of Premi lab is designing next generation, drug like sunscreen compounds. We design and screen novel plant based and synthetic compounds to identify the ones that are non-toxic, non-photosensitizers, potent anti-oxidants, and efficient in blocking incidental and delayed DNA damage induced by exposure to ultraviolet radiation (UV). To achieve this, we have designed several innovative, chemical, and cell-based methods which include measurement of triplet energies of carbonyls and other chemically excited species, DNA ELISA, interaction between DNA and melanin carbonyls, and effect of this interaction on gene expression. Ultimate goal is to design next generation skin-care products which are cosmetic as well as therapeutic. To achieve this, we are funded by NIH, DoD, and also by cosmetic and pharmaceutical industries.

• Srivastava J, Young MM, Yadav VK, Phadatare PR, Meyer TA, Chaudhuri RK, Premi S. The Role of Acetyl Zingerone and Its Derivatives in Inhibiting UV-Induced, Incident, and Delayed Cyclobutane Pyrimidine Dimers. Antioxidants (Basel). 2023 Jan.12(2). Pubmedid: 36829837. Pmcid: PMC9952391.
• Ramos LD, Gomes TMV, Quintiliano SAP, Premi S, Stevani CV, Bechara EJH. Biological Schiff bases may generate reactive triplet carbonyls and singlet oxygen: A model study. Free Radical Bio Med. 2022 Oct.191:97-104. Pubmedid: 36049617.
• Lawrence KP, Delinasios GJ, Premi S, Young AR, Cooke MS. Perspectives on Cyclobutane Pyrimidine Dimers-Rise of the Dark Dimers. Photochem Photobiol. 2022 May.98(3):609-616. Pubmedid: 34706095.
• Premi S, Qin Y, Ahmad N. Editorial: Mechanisms of resistance to the targeted therapy and immunotherapy in cutaneous melanoma. Front Oncol. 2022 Aug.12:1016901. Pubmedid: 36110949. Pmcid: PMC9469656.
• Amente S, Scala G, Majello B, Azmoun S, Tempest HG, Premi S, Cooke MS. Genome-wide mapping of genomic DNA damage: methods and implications. Cell Mol Life Sci. 2021 Nov.78(21-22):6745-6762. Pubmedid: 34463773. Pmcid: PMC8558167.
• Chaudhuri RK, Meyer T, Premi S, Brash D. Acetyl zingerone: An efficacious multifunctional ingredient for continued protection against ongoing DNA damage in melanocytes after sun exposure ends. Int J Cosmet Sci. 2020 Feb.42(1):36-45. Pubmedid: 31538664. Pmcid: PMC7004018.
• Premi S. Role of Melanin Chemiexcitation in Melanoma Progression and Drug Resistance. Front Oncol. 2020 Aug.10:1305. Pubmedid: 32850409. Pmcid: PMC7425655.
• Premi S, Han L, Mehta S, Knight J, Zhao D, Palmatier MA, Kornacker K, Brash DE. Genomic sites hypersensitive to ultraviolet radiation. Proc Natl Acad Sci U S A. 2019 Nov.116(48):24196-24205. Pubmedid: 31723047. Pmcid: PMC6883822.
• Premi S, Brash DE. Unanticipated role of melanin in causing carcinogenic cyclobutane pyrimidine dimmers. Mol Cell Oncol. 2016 Jan.3(1):e1033588. Pubmedid: 27308551. Pmcid: PMC4845191.
• Premi S, Brash DE. Chemical excitation of electrons: A dark path to melanoma. DNA Repair (Amst). 2016 Aug.44:169-177. Pubmedid: 27262612. Pmcid: PMC4958542.
• Premi S, Wallisch S, Mano CM, Weiner AB, Bacchiocchi A, Wakamatsu K, Bechara EJ, Halaban R, Douki T, Brash DE. Photochemistry. Chemiexcitation of melanin derivatives induces DNA photoproducts long after UV exposure. Science. 2015 Feb.347(6224):842-847. Pubmedid: 25700512. Pmcid: PMC4432913.
• Zhang R, Premi S, Kilic SS, Bacchiocchi A, Halaban R, Brash DE. Clonal growth of human melanocytes using cell-free extracellular matrix. Pigment Cell Melanoma Res. 2013 Nov.26(6):925-927. Pubmedid: 24034857. Pmcid: PMC4086752.
• Muthusamy V, Premi S, Soper C, Platt J, Bosenberg M. The hematopoietic stem cell regulatory gene latexin has tumor-suppressive properties in malignant melanoma. J Invest Dermatol. 2013 Jul.133(7):1827-1833. Pubmedid: 23364479. Pmcid: PMC3683103.
• Premi S, Srivastava J, Epplen JT, Ali S. AZFc region of the Y chromosome shows singular structural organization. Chromosome Res. 2010 Jun.18(4):419-430. Pubmedid: 20373140.
• Premi S, Srivastava J, Panneer G, Ali S. Startling mosaicism of the Y-chromosome and tandem duplication of the SRY and DAZ genes in patients with Turner Syndrome. PLoS One. 2009 Jun.3(11):e3796. Pubmedid: 19030103. Pmcid: PMC2582957.
• Srivastava J, Premi S, Kumar S, Ali S. Expressional dynamics of minisatellite 33.15 tagged spermatozoal transcriptome in Bubalus bubalis. BMC Genomics. 2009 Jul.10:303. Pubmedid: 19583837. Pmcid: PMC2713999.
• Premi S, Srivastava J, Chandy SP, Ali S. Unique signatures of natural background radiation on human Y chromosomes from Kerala, India. PLoS One. 2009 Apr.4(2):e4541. Pubmedid: 19242544. Pmcid: PMC2644265.
• Srivastava J, Premi S, Kumar S, Ali S. Organization and differential expression of the GACA/GATA tagged somatic and spermatozoal transcriptomes in Buffalo Bubalus bubalis. BMC Genomics. 2008 Mar.9:132. Pubmedid: 18366692. Pmcid: PMC2346481.
• Srivastava J, Premi S, Kumar S, Parwez I, Ali S. Characterization of Smoc-1 uncovers two transcript variants showing differential tissue and age specific expression in Bubalus bubalis. BMC Genomics. 2007 Nov.8:436. Pubmedid: 18042303. Pmcid: PMC2235864.
• Premi S, Srivastava J, Chandy SP, Ali S. AZFc somatic microdeletions and copy number polymorphism of the DAZ genes in human males exposed to natural background radiation. Hum Genet. 2007 May.121(3-4):337-346. Pubmedid: 17308897.
• Srivastava J, Premi S, Garg LC, Ali S. Organizational and expressional uniqueness of a testis-specific mRNA transcript of protooncogene c-kit receptor in water buffalo Bubalus bubalis. DNA Cell Biol. 2006 Sep.25(9):501-513. Pubmedid: 16989573.
• Pathak D, Premi S, Srivastava J, Chandy SP, Ali S. Genomic instability of the DYZ1 repeat in patients with Y chromosome anomalies and males exposed to natural background radiation. DNA Res. 2006 Jun.13(3):103-109. Pubmedid: 16980714.
• Srivastava J, Premi S, Pathak D, Ahsan Z, Tiwari M, Garg LC, Ali S. Transcriptional status of known and novel genes tagged with consensus of 33.15 repeat loci employing minisatellite-associated sequence amplification (MASA) and real-time PCR in water buffalo, Bubalus bubalis. DNA Cell Biol. 2006 Jan.25(1):31-48. Pubmedid: 16405399.
• Premi S, Srivastava J, Chandy SP, Ahmad J, Ali S. Tandem duplication and copy number polymorphism of the SRY gene in patients with sex chromosome anomalies and males exposed to natural background radiation. Mol Hum Reprod. 2006 Feb.12(2):113-121. Pubmedid: 16510537.
• Pathak D, Srivastava J, Premi S, Tiwari M, Garg LC, Kumar S, Ali S. Chromosomal localization, copy number assessment, and transcriptional status of BamHI repeat fractions in water buffalo Bubalus bubalis. DNA Cell Biol. 2006 Apr.25(4):206-214. Pubmedid: 16629593.

• Title: Novel role of melanin-carbonyls in progression of NRAS mutant melanoma
  Sponsor: Nat Institutes of Health
  PI (Contact): Premi, S.
• Title: Investigate the Mechanisms Responsible for Inhibition of CPDs by AZ and Its Analogs
  Sponsor: Sytheon, Ltd.
  PI: Premi, S.