Laboratory of Maria Agustina Battistone, PhD

Overview

The Battistone Laboratory explores the molecular basis of mucosal immunity in the urogenital tract and applies the knowledge acquired through basic research to identify new diagnostic and therapeutic targets for male infertility and acute kidney injury (AKI). We are particularly intrigued by the paradigm-shifting discovery that epithelial proton-secreting cells modulate the immune system, and we explore the role of these cells in inflammation, which leads to epididymitis and AKI.

Infertility is a prevalent, disheartening condition for couples and individuals worldwide, and many cases of male infertility are thought to stem from immunological causes or are classified as idiopathic. Successful sperm maturation and storage rely on a unique immunological balance that protects the male reproductive organs from invading pathogens and spermatozoa—which appear during puberty after the immune definition of “self” has been established—from a destructive autoimmune response. We elucidate how epithelial clear cells communicate with immunocytes to contribute to the “immune privileged” environment that is optimal for sperm maturation and storage in the epididymis.

Uncontrolled inflammation is a leading cause of AKI, a frequent and fatal complication of hospitalized patients. Unfortunately, AKI is often diagnosed too late, and there is no specific cure. We address these needs by building upon a previously unrecognized role for renal proton-secreting epithelial cells, so-called intercalated cells in the onset of AKI. We showed the participation of the P2Y14 receptor in intercalated cells in inflammation that follow an ischemic renal injury. This groundbreaking finding pointed toward P2Y14 as a therapeutic target for the prevention/attenuation of AKI. Furthermore, collaborating with clinical investigators in the Nephrology Division at Mass General, we found that the P2Y14 ligand UDP-glucose is a urinary biomarker of AKI in patients undergoing cardiac surgery who developed AKI. 

Meet the Team

Maria Agustina Battistone, PhD
Assistant Professor of Medicine, Massachusetts General Hospital, Harvard Medical School

Angela Chen, BS
Research Assistant

Micah Cornelia Purba, BA
Graduate Student

Research Projects

Epithelial Dynamics and Epididymal Mucosal Immunity

Infertility affects 12%–15% of couples in the world, and male factors are involved in 40%–50% of these cases, half of which are classified as idiopathic. Spermatozoa acquire motility and fertilizing power during their transit through the epididymis, a long tube located downstream of the testis. One of the most intriguing and understudied aspects of male reproductive physiology is the ability of the epididymis to prevent the development of immune responses against autoantigenic spermatozoa while initiating very efficient immune responses against pathogens.

Our laboratory studies how epithelial cells work together with immune cells to protect spermatozoa against pathogens and autoimmunity and contribute to the immune-privileged environment of the epididymis. The long-term goal is to develop new strategic therapies for common disorders, such as male infertility and epididymitis, and to identify novel targets for male contraception.

Proton-secreting Intercalated Cells and Acute Kidney Injury

Acute kidney injury is a frequent and fatal complication in hospitalized patients. Unfortunately, acute kidney injury is currently diagnosed only after a renal injury has occurred, and there is no specific cure for this deadly complication. Therefore, there is a clear need for the development of early markers of kidney injury and an associated therapy to reverse or prevent this complication.

We address this clinical gap by leveraging novel mechanisms by which epithelial proton-secreting intercalated cells communicate damage to immunocytes in the kidney. Uncontrolled inflammation is a leading cause of acute kidney injury. Ultimately, our research will fill gaps to understand the pathogenesis of renal failure.

Publications

View all publications of the Battistone Lab

Selected Publications:

• Barrachina F, Battistone MA, Castillo J, Mallofré C, Jodar M, Breton S, Oliva R. Sperm acquire epididymis-specific proteins through epididymosomes. Hum Reprod. 2022 Apr 1;37(4):651-668. PMID: 35137089.
• Breton S and Battistone MA. Unexpected participation of intercalated cells in renal inflammation and acute kidney injury. Nephron. 2021 Oct 15:1-6. PMID: 34657041.
• Mendelsohn AC, Sanmarco LM, Spallanzani RG, Brown D, Quintana F, Breton S, Battistone MA. From initial segment to cauda: A regional characterization of mouse epididymal CD11c+ mononuclear phagocytes based on immune phenotype and function. Am J Physiol Cell Physiol: Cell Physiol. 2020 Dec 1;319(6): C997-C1010. PMID: 32991210.
• Battistone MA, Mendelsohn AC, Spallanzani RG, Allegretti AG, Liberman RN, Sesma J, Kalim S, Wall SM, Bonventre JV, Lazarowski ER, Brown D, Breton S. Proinflammatory P2Y14 receptor inhibition protects against ischemic acute kidney injury in mice. J Clin Invest. 2020 Jul 1;130(7):3734-3749. PMID: 32287042.
• Battistone MA, Mendelsohn AC, Spallanzani RG, Brown D, Nair AV, Breton S. Region-specific transcriptomic and functional signatures of mononuclear phagocytes in the epididymis. Mol. Hum. Reprod. 2020 Jan 1;26(1):14-29. PMID: 31778536.
• Battistone MA, Spallanzani RG, Mendelsohn AC, Capen D, Nair AV, Brown D, Breton S. Novel role of proton-secreting epithelial cells in sperm maturation and mucosal immunity. J Cell Sci. 2019 Nov 18;133(5):jcs233239. PMID: 31636115.

Research Positions

We accept fellows and visiting scientists. Should you have any questions or are interested in joining our team, please contact Dr. Battistone.

Maria A. Battistone, PhD
Email: mbattistone@mgh.harvard.edu 

News

Maria Agustina Battistone, PhD, received the 2022 Claflin Distinguished Scholars Award from the Massachusetts General Hospital Executive Committee on Research. This funding increases opportunities for women to advance to senior positions in academic medicine.

Ferran Barrachina Villalonga, PhD, received the 2022 Lonnie D. Russell Merit Award at the 47th American Society of Andrology (ASA) Annual Meeting (La Jolla, California, May 7-10, 2022). This award is conferred to the best original laboratory or clinical research report in andrology presented at the meeting.

Ferran Barrachina Villalonga, PhD, received the 2022 NIH-Travel Award to attend the 47th ASA Annual Meeting (La Jolla, California, May 7-10, 2022).