Sensing extra and intracellular stressors by renal and immune cells: new insights into signal reception and transduction, and their relevance for understanding renal diseases

• Grant number: 23/07482-2
• Support Opportunities: Research Projects - Thematic Grants
• Start date: July 01, 2024
• End date: June 30, 2029
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Niels Olsen Saraiva Câmara
• Grantee: Niels Olsen Saraiva Câmara
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Pesquisadores principais:( Atuais ): Alvaro Pacheco e Silva Filho ; Maria Oliveira de Souza
• Pesquisadores principais:( Anteriores ): Alessandra Pontillo
• Associated researchers: Alessandra Pontillo ; Amaro Nunes Duarte Neto ; Bernardo Simoes Franklin ; Carlos Escande ; Leandro Machado Colli ; Michael F Romero ; Renato Costa Monteiro Filho ; Rildo Aparecido Volpini ; Sofia de Oliveira ; Sue Tsai ; Tárcio Teodoro Braga ; Tiago Albertini Balbino ; Vinicius de Andrade Oliveira
• Associated research grant(s): 24/08997-9 - Multi-user equipment approved in grant 23/07482-2: microscope Celldiscoverer 7 KMAT, AP.EMU
• Associated scholarship(s): 25/05907-1 - HO-1 and ferroptosis: a new understanding of how oxidative stress from the tumor microenvironment modulates immune cells and contributes to resistance to immunotherapy, BP.DD; 25/01495-0 - Impact of IL-11 on Mitochondrial Fitness and Skin Inflammation Associated with Aging, BP.DD; 24/10027-8 - Migration pattern of MAIT cells between blood circulation and omental adipose tissue associated with changes in intestinal microbiota in the inflammatory context of obesity associated with type 2 diabetes mellitus, BP.IC; + associated scholarships 24/21710-0 - Role of the HIF1¿/AhR axis in regulatory T cells mitochondrial dynamics during Inflammatory Bowel Disease using an autologous organoid co-culture model., BP.PD; 24/17216-0 - Maintenance of the zebrafish facility at the Transplantation Immunobiology Laboratory., BP.TT; 24/18223-0 - Application of the Cre-loxP system for generation and maintenance of different lines of transgenic mice, BP.TT; 24/12992-2 - The role of the hypoxia sensor HIF-1 alpha in podocytes: a link between cell metabolism and kidney injury., BP.IC; 24/10650-7 - The role of DNA damage and of the XPC protein in the activation and function of macrophages, BP.IC; 24/15982-8 - Implementation and standardization of image acquisition and analysis for cell phenotype screening using high-throughput microscopy, BP.TT; 24/13863-1 - Role of mitochondria-associated membranes (MAMs) in neutrophils under diabetic kidney injury., BP.PD; 22/14364-3 - The role of the TRPM5 receptor in the activation and differentiation of CD4+ T cells and its relevance in an experimental model of intestinal inflammation, BP.DR - associated scholarships

Abstract

Chronic kidney diseases are still a leading cause of death worldwide. Thus, the need for new treatment approaches is urgent. Here, we aim to unravel new sensing mechanisms for organelles on renal and immune cells and how the external and internal perception of unbalance is involved in responses which triggers injury, influences repair, and promotes renal tissue fibrosis. We hypothesize that organelles have a central role on sensing and transducing signals from different source. To do that, we intend to use in vivo (mouse and zebrafish models), in vitro (cell culture, organoids), in silico (scRNAseq, omics) and ex-vivo (Human samples) approaches, employing commonly used experimental methods to evaluate cell function as well as cutting-edge technologies (e.g., Organ-on-chip, single cell RNA sequencing - scRNAseq; Forster resonance energy transfer-FRET; CRISPR-Cas9; the newly developed imaging technique MINFLUX). We believe that understanding the new functions attributed to organelles could be a potential new strategy to treat kidney diseases. (AU)

Scientific publications

(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)

BERTRAM, JOHN F.; CULLEN-MCEWEN, LUISE A.; ANDRADE-OLIVEIRA, VINICIUS; CAMARA, NIELS OLSEN SARAIVA. The intelligent podocyte: sensing and responding to a complex microenvironment. NATURE REVIEWS NEPHROLOGY, v. 21, n. 7, p. 14-pg., 2025-05-08. (19/14755-0, 23/07482-2)

DE LIMA, JEAN; LEITE, JEFFERSON ANTONIO; BASSO, PAULO JOSE; GHIROTTO, BRUNO; DA SILVA, ELOISA MARTINS; MENEZES-SILVA, LUISA; HIYANE, MEIRE IOSHIE; GOES, CAROLINA PURCELL; COUTINHO, LUIZ LEHMANN; OLIVEIRA, VINICIUS DE ANDRADE; et al. Sirtuin 1 regulates the phenotype and functions of dendritic cells through Ido1 pathway in obesity. CELL DEATH & DISEASE, v. 15, n. 10, p. 17-pg., 2024-10-18. (17/05264-7, 18/04326-1, 19/07820-0, 23/07482-2, 19/19435-3)

OLIVEIRA, SAMUEL DOS SANTOS; DA SILVA, JOAO VINICIUS HONORIO; VIEIRA, RAQUEL DE SOUZA; MOREIRA, LUIS FELIPE SERRA; BANDEIRA, PEDRO HENRIQUE ARAUJO; RAMOS, BEATRIZ LEOCATA; SILVA, MARCO ANTONIO ATAIDE; CAMARA, NIELS OLSEN SARAIVA. SARM1: a key multifaceted component in immunoregulation, inflammation and neurodegeneration. FRONTIERS IN IMMUNOLOGY, v. 16, p. 11-pg., 2025-05-13. (23/07482-2, 22/16176-0)