Involvement of the photosensitive and temporal controlling systems in the development, progression, and metastasis of malignant melanoma: an investigation of novel therapeutic targets

• Grant number: 18/16511-8
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: April 01, 2019
• End date: October 14, 2020
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Ana Maria de Lauro Castrucci
• Grantee: Leonardo Vinícius Monteiro de Assis
• Host Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The photosensitive system of the skin has been known for more than 20 years; however, only in 2011 a significant advance regarding its functionality started to be reported. Our research group has been working in a pioneering fashion in the field. Thus far we have demonstrated that the skin photosensitive system not only participates in UVA-induced immediate pigment darkening, but also as thermo-sensor, which feeds the molecular clock of normal and malignant melanocytes. Within this line, the temporal control system of the skin has an elegant working mechanism whose role is evident in the physiological scenario; however, its participation in pathological conditions - more specifically in cancer - is still poorly understood. We have provided strong evidence that the molecular components of the clock are downregulated in malignant melanocytes; thus, demonstrating the establishment of chronodisruption in melanoma cancer when compared to health tissue. We have also shown in a pioneering fashion that a non-metastatic melanoma leads to chronodisruption in distant organs, and that in patients BMAL1 is a positive prognostic factor that can be used as a tool to discriminate patients that could benefit from immunotherapy regimes. Taken altogether, this project has the goal to elucidate the participation of melanopsin in the development, progression, and metastases of melanoma cancer through the usage of melanopsin knockout cell line and/or animals and its putative interaction with the skin biological clock. Several experimental protocols will be employed to reach this goal. Bioinformatics analysis will be performed in public database in order to establish targets for in vitro validation. In addition, this project will evaluate the role of central and peripheral clocks in the development of melanoma through the usage of genetically modified animals. To reach its goal this project has a multidisciplinary, international, and collaborative team as well as it will use elegant cellular models and genetically modified animals whose physiological phenomena will be evaluated by advanced techniques of molecular biology. The ultimate aim is to establish the photosensitive and molecular clock systems of the skin as potential therapeutic targets for the treatment of melanoma cancer. (AU)

Scientific publications

(9)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

SUA-CESPEDES, CRISTHIAN D.; DAVID, DANIELA DANTAS; SOUTO-NETO, JOSE A.; LIMA, OTONIEL GONCALVES; MORAES, MARIA NATHALIA; DE ASSIS, LEONARDO V. MONTEIRO; CASTRUCCI, ANA MARIA DE LAURO. Low Temperature Effect on the Endocrine and Circadian Systems of Adult Danio rerio. FRONTIERS IN PHYSIOLOGY, v. 12, NOV 24 2021. (18/23043-0, 18/16511-8, 17/26651-9, 18/14728-0, 17/24615-5, 18/23915-8)

HERMIDORFF, MILLA MARQUES; MONTEIRO DE ASSIS, LEONARDO VINICIUS; RODRIGUES, JOEL ALVES; SOARES, LEONCIO LOPES; GUERRA ANDRADE, MILTON HERCULES; NATALI, ANTONIO JOSE; ISOLDI, MAURO CESAR. Mineralocorticoid receptor antagonists lead to increased adenosine bioavailability and modulate contractile cardiac parameters. HEART AND VESSELS, v. 35, n. 5, p. 719-730, MAY 2020. (13/24337-4, 18/16511-8)

MIRANDA, DENISE COUTINHO DE; FARIA, GABRIELA DE OLIVEIRA; HERMIDORFF, MILLA MARQUES; SILVA, FERNANDA CACILDA DOS SANTOS; ASSIS, LEONARDO VINICIUS MONTEIRO DE; ISOLDI, MAURO CESAR. Pre- and Post-Conditioning of the Heart: An Overview of Cardioprotective Signaling Pathways. CURRENT VASCULAR PHARMACOLOGY, v. 19, n. 5, p. 499-524, 2021. (18/16511-8)

DE ASSIS, LEONARDO VINICIUS MONTEIRO; MORAES, MARIA NATHALIA; MENDES, DAVI; SILVA, MATHEUS MOLINA; MENCK, CARLOS FREDERICO MARTINS; CASTRUCCI, ANA MARIA DE LAURO. Loss of Melanopsin (OPN4) Leads to a Faster Cell Cycle Progression and Growth in Murine Melanocytes. CURRENT ISSUES IN MOLECULAR BIOLOGY, v. 43, n. 3, p. 1436-1450, DEC 2021. (18/16511-8, 17/24615-5, 17/26651-9, 17/18781-0, 19/19435-3, 18/14728-0, 17/24217-0)

MONTEIRO DE ASSIS, LEONARDO VINICIUS; MENDES, DAVI; SILVA, MATHEUS MOLINA; KINKER, GABRIELA SARTI; PEREIRA-LIMA, ISABELLA; MORAES, MARIA NATHALIA; MARTINS MENCK, CARLOS FREDERICO; DE LAURO CASTRUCCI, ANA MARIA. Melanopsin mediates UVA-dependent modulation of proliferation, pigmentation, apoptosis, and molecular clock in normal and malignant melanocytes. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, v. 1867, n. 10, OCT 2020. (14/27287-0, 19/19435-3, 13/24337-4, 17/24615-5, 12/50214-4, 18/16511-8, 17/26651-9, 17/18781-0, 18/14728-0, 17/24217-0)

FORNI, MARIA FERNANDA; ALBERTO DOMINGUEZ-AMOROCH, OMAR; MONTEIRO DE ASSIS, LEONARDO VINICIUS; KINKER, GABRIELA SARTI; MORAES, MARIA NATHALIA; DE LAURO CASTRUCCI, ANA MARIA; SARAIVA CAMARA, NIELS OLSEN. An Immunometabolic Shift Modulates Cytotoxic Lymphocyte Activation During Melanoma Progression in TRPA1 Channel Null Mice. FRONTIERS IN ONCOLOGY, v. 11, MAY 10 2021. (18/16511-8, 18/14728-0, 17/16711-4, 17/26651-9, 17/24615-5)

MONTEIRO DE ASSIS, LEONARDO VINICIUS; LACERDA, JOSE THALLES; MORAES, MARIA NATHALIA; DOMINGUEZ-AMOROCHO, OMAR ALBERTO; KINKER, GABRIELA SARTI; MENDES, DAVI; SILVA, MATHEUS MOLINA; MARTINS MENCK, CARLOS FREDERICO; SARAIVA CAMARA, NIELS OLSEN; DE LAURO CASTRUCCI, ANA MARIA. Melanopsin (Opn4) is an oncogene in cutaneous melanoma. COMMUNICATIONS BIOLOGY, v. 5, n. 1, p. 15-pg., 2022-05-13. (19/19435-3, 19/25129-2, 17/24217-0, 17/26651-9, 18/16511-8, 12/50214-4, 18/14728-0, 17/24615-5, 17/18781-0, 20/04524-8, 13/24337-4, 17/16711-4)

LACERDA, JOSE THALLES; GOMES, PATRICIA R. L.; ZANETTI, GIOVANNA; MEZZALIRA, NATHANA; LIMA, OTONIEL G.; DE ASSIS, LEONARDO V. M.; GULER, ALI; CASTRUCCI, ANA MARIA; MORAES, MARIA NATHALIA. Lack of TRPV1 Channel Modulates Mouse Gene Expression and Liver Proteome with Glucose Metabolism Changes. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 23, n. 13, p. 24-pg., 2022-07-01. (17/24615-5, 21/01659-2, 14/16412-9, 20/04524-8, 18/23915-8, 18/16511-8, 13/02131-5, 12/50214-4, 18/14728-0, 17/26651-9, 21/09923-0)

SUA-CESPEDES, CRISTHIAN; LACERDA, JOSE THALLES; ZANETTI, GIOVANNA; DAVID, DANIELA DANTAS; MORAES, MARIA NATHALIA; DE ASSIS, LEONARDO V. M.; CASTRUCCI, ANA MARIA L.. Melanopsin (OPN4) is a novel player in skin homeostasis and attenuates UVA-induced effects. JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY, v. 242, p. 15-pg., 2023-04-03. (16/00696-3, 13/07937-8, 19/19005-9, 21/01659-2, 17/26651-9, 18/23043-0, 18/16511-8, 12/50214-4, 12/12663-1, 18/14728-0, 17/24615-5, 20/04524-8, 14/16412-9)