Single cell analyses and non-linear optics approaches of prostate biology

• Grant number: 21/02303-7
• Support Opportunities: Research Projects - Thematic Grants
• Start date: May 01, 2022
• End date: April 30, 2027
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Hernandes Faustino de Carvalho
• Grantee: Hernandes Faustino de Carvalho
• Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• City of the host institution: Campinas
• Principal investigators: Carlos Lenz Cesar
• Associated researchers: Fabiano Beraldi Calmasini ; Fernanda Cristina Alcantara dos Santos
• Associated research grant(s): 22/03880-0 - WFDC1 - Role in cardiovascular system development and potential applications in translational medicine, AP.R
• Associated scholarship(s): 25/26230-0 - Interaction between killer macrophages and prostatic epithelial cells: analyses of oxidative stress in 3D cultures, BP.IC; 25/17342-9 - Prostatic cell types and subtypes in diffent experimental setups, BP.PD; 25/13087-4 - Single cell analysis of cell subpopulations and their dynamics in the ventral prostate after castration, BP.TT; 24/03550-6 - Obtaining recombinant ps20 by heterologous expression in eukaryotic cells, BP.TT; 23/15144-0 - scRNAseq analysis of the prostate development, BP.PD

Abstract

The prostate is susceptible to different diseases including the prostatitis, benign prostate hyperplasia and prostate cancer. Prostate cancer will affect 12.5% of men in all ages and 50% of men at the age 85. Benign prostate hyperplasia will affect a larger number of younger men. Our interest is to study prostate physiology at the cell and molecular biology levels, to better understand this organ's and its different cell types' behavior in diseases.This project is divided in four subprojects including (a)Prostate development, focusing on the cell-cell interactions taking place at the epithelial growth tip, in particular in the relationship between the differentiation of smooth muscle cells and the settlement of p63+ cells along the epithelial structure, considering the MMPs. Aspects of the mechanics of the development will be obtained from the analysis of smooth muscle cells differentiation/contractility and the deposition of collagen fibers.(b)The organ's response to castration/orchiectomy, specially in the characterization of gene networks capable to orchestrate the tissue modification taking place in the hypoandrogenic environment at the level of single cells, focusing on the expression of collagenases (MMP-1, MMP-8 and MMP-11.(c)The inflammation affecting the gland in experimental autoimmune prostatitis and in the response to diets containing different types of fatty acids, with emphasis on the macrophages and, among them, the M1142 macrophages we have previously described; this subproject will include an analysis of the microbiota, seeking for possible association with systemic and tissue inflammatory markers and(d)The structure and function of the protein ps20, expressed by smooth muscle cells, with attention to the possible activity as serine-proteinase inhibitor and other physiological functions, such as the relaxation of smooth muscle cells. In each of these subprojects, we will set the role of different cell types and their interactions, as well as identification of molecules involved, seeking to define the molecular mechanisms involved. Beyond the epithelial and stromal subtypes, we will be engaged with the identification of immune system's cells, particularly the macrophages, performing functions in the different phenomena associated with the response to castration and in the experimental autoimmune prostatitis. Our approach to these themes will be centered in two major technologies. The first is the analysis of single cell transcriptomes (scRNAseq). The second is the use of non-linear optics-based microscopies (SHG, FLIM, CARS). Implementing scRNAseq is the major methodological challenge to this project. The second is part of our expertise. In some cases, we will associate with other laboratories to perform proteomics, metabolomics and metagenomics. We will be engaged in the training of personnel and in science diffusion, considering the obtained results/data, as well technological and therapeutical progresses in the scope of the project. (AU)

Scientific publications

(4)

(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)

SANCHES, BRUNO DOMINGOS AZEVEDO; TAMARINDO, GUILHERME HENRIQUE; DA SILVA, ALANA DELLA TORRE; AMARO, GUSTAVO MATHEUS; DOS SANTOS MALDARINE, JULIANA; DOS SANTOS, VITORIA ALARIO; GUERRA, LUIZ HENRIQUE ALVES; BARALDI, CAROLINA MARQUES BEDOLO; GOES, REJANE MAIRA; TABOGA, SEBASTIAO ROBERTO; et al. Stromal cell-derived factor 1 (SDF-1) increases the number of telocytes in ex vivo and in vitro assays. Histochemistry and Cell Biology, v. N/A, p. 15-pg., 2023-07-20. (21/02303-7, 18/08945-8)

HADAD, ANDR; FRANCA, VICTOR L. B.; AMARAL, JACKSON L.; CARVALHO, HERNANDES F.; FREIRE, VALDER N.. Quantum biochemistry characterization of representative conformations of the sex hormone-binding globulin monomer bound to estradiol, dihydrotestosterone and testosterone. JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, v. 255, p. 12-pg., 2025-01-25. (21/02303-7)

SANCHES, BRUNO D. A.; ROCHA, LARA C.; NETO, J. PIMENTEL; BEGUELINI, MATEUS RODRIGUES; CIENA, ADRIANO P.; CARVALHO, HERNANDES F.. Telocytes of the male reproductive system: dynamic tissue organizers. FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY, v. 12, p. 11-pg., 2024-10-14. (21/02303-7)

SANTOS, NILTON J.; MOSELE, FRANCIELLE C.; BARQUILHA, CAROLINE N.; BARBOSA, ISABELA C.; LIMA, FLAVIO DE OLIVEIRA; BARBOSA, GUILHERME OLIVEIRA; CARVALHO, HERNANDES F.; DELELLA, FLAVIA KARINA; FELISBINO, SERGIO LUIS. SLIT/ROBO Pathway and Prostate Cancer: Gene and Protein Expression and Their Prognostic Values. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 26, n. 11, p. 13-pg., 2025-05-30. (19/19644-1, 21/02303-7)