Mayo Clinic researcher Michael F. Romero, Ph.D., leads a physiology lab focused on the movement and balance of ions and solutes across cell membranes in health and disease. Ions are electrically charged atoms or groups of atoms; solutes are other particles dissolved into a solution — in this case, the human bloodstream. Dr. Romero's lab aims to better understand the molecular and cellular physiology of normal ion and solute transport in order to pinpoint the physiological causes of kidney disease and other related diseases and conditions, including those tied to changes in genes. In particular, the lab looks at particles including:
- Sodium ions (Na+).
- Bicarbonate (HCO3 ).
- Hydrogen ions (H+), also known as pH.
- Chloride ions (Cl-).
- Carbon dioxide (CO2).
A healthy human kidney filters the body's entire volume of blood every five minutes — approximately 2,000 liters a day. Tubules in the kidney, which are called epithelia or nephrons, maintain health by reclaiming both water and more than 99% of all these solutes from the blood. Therefore, even small changes in absorption or secretion can cause kidney disease and other conditions such as:
- Kidney stones.
- Polycystic kidney disease.
The kidney does not work alone, and most of the proteins that move these solutes around the body are also found in other organs. This is why kidney disease is often associated with heart disease, diabetes, breathing disorders and intestinal disorders as well as brain, vision and even hearing disorders.
- Na+-coupled bicarbonate transporters. The Romero lab studies the structure and function of Na+-coupled bicarbonate transporters in the kidney, gut and other organs. The research team studies the biophysics of these transporters at the level of the cell, tissue and whole body.
Dr. Romero helped to pioneer this area of research by using expression cloning to isolate the first cDNA for a Na+ bicarbonate cotransporter. His original work sourced the same salamander (Ambystoma tigrinum) kidneys as were originally studied to describe this activity in the kidney. These salamanders are now becoming excellent models not only for limb regeneration but also regeneration of internal organs such as the liver and kidney.
- Drosophila model and tools. Dr. Romero has led research to develop a model of kidney stones and kidney disease in Drosophila, commonly known as fruit flies, as well as Drosophila tools to study the kidneys and gut. His exploration of the S1c26a6 electrogenic transporter's function in lower species showed that nonmammalian Slc26a5, or prestin, has transport functions. Knowing that this protein was most highly expressed in Drosophila gut tissues and renal tissues called Malpighian tubules, Dr. Romero's research team created a fruit fly model of calcium oxalate kidney stones. This was a crucial breakthrough that greatly accelerated research, because mammals form stones slowly, over weeks or months, while fruit flies form crystals in less than 60 minutes. This model allows testing of genes implicated in kidney stone formation to help determine disease processes as well as cause-and-effect relationships.
- Preclinical ultrasound imaging. Expanding on knowledge of ocular physiology, and using optical coherent tomography, fluorescent angiography and electroretinography, Dr. Romero's team characterized vision in NBCe1- knockout animals. This work laid the foundation for using ultrasound to image and measure the physical properties and function of the kidney, heart and liver.
- Tools to measure cell and kidney function. Dr. Romero's lab builds molecular and hardware tools to measure kidney function at the cell and organ level. As the lab developed cell, fly and mouse models, it also developed genetically encoded ion sensors. These fluorescent sensors allow the research team to visually follow the function of freshly isolated tissues from the lab's genetic models. The team has also developed and tested new and unique ways to measure kidney function, such as glomerular filtration rate (GFR), in animals and humans.
- Transporters and channels. Dr. Romero leads research on the expression and function of transporters and channels as well as on their unique functions. The Romero lab's transport studies and collaborations have revealed transporters and channels that are important in providing care to patients with eye conditions, central nervous system concerns, inflammatory bowel disease or urinary continence.
Additionally, Dr. Romero's research team has applied its biophysical experience to other transporters to document new transport modes. Recent collaborations have highlighted that aquaglyceroporins in euryhaline fish and humans can transport borate, an anion of boron. This allows fish to eliminate borate from their blood, but the physiological role in mammals and humans is not yet known.
Significance to patient care
Dr. Romero's research holds the potential to improve patient care in multiple ways. Understanding the molecular and cellular physiology of normal solute transport is critical to figuring out the underlying causes of kidney disease and related illnesses, including acidosis, hypertension, diabetes, polycystic kidney disease, and acute and chronic kidney disease — and also may help understand these diseases when they are tied to genetic changes as well.
Additionally, by improving the understanding of metabolic control in pancreatic beta-cells, Dr. Romero aims to prevent metabolic stress that ultimately results in type 2 diabetes.
Further, by developing an in vivo, direct system to measure GFR, Dr. Romero and colleagues hope to provide new and better tools for routine clinical assessment as well as remote kidney function monitoring. This tool also should help make drug and chemotherapeutic dosing even more accurate and may help to alleviate side effects.
- Fellow, American Physiological Society, 2022-present.
- Editorial boards.
- Hypertension, 2022-present.
- Associate editor, Kidney360, 2019-present.
- American Journal of Physiology — Renal, 2001-2019.
- Journal of Biological Chemistry, 2007-2012.
- American Journal of Physiology — Gastrointestinal and Liver, 2000-2003.
- Faculty, Tutored Research and Education for Kidney Scholars (TREKS) program and Kidney Stones Module of "Origins of Renal Physiology" fellowship course, Mount Desert Island Biological Laboratory, American Society of Nephrology, 2016-present.
- Member, Scientific Advisory Committee, Oxalosis and Hyperoxaluria Foundation, 2013-present.
- National Institutes of Health panels.
- Special emphasis panel member: Diabetes and Digestive and Kidney Diseases study section, 2021, 2023; Cell Biology, Developmental Biology, and Bioengineering Fellowships, 2022; Development of Animal Models and Related Materials, 2022; U2C/TL1 area grants for the Division of Kidney, Urologic, and Hematologic Diseases, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), 2022; Urology and Urogynecology, 2020; Chronic Disease and the Reduction of Health, Disparities Within the Mission of NIDDK, 2020; Career development awards, 2010; NIDDK Special Emphasis P01 panel, 2010.
- Member, Diabetes and Digestive and Kidney Diseases study section, National Institutes of Health, 2013-2019.
- Member, Cellular and Molecular Biology of the Kidney study section, 2006-2010.
- Member, Stem Cell Transplantation (Basic Science 6), Fellowship Committee, American Heart Association, 2020-2022.
- Conference organizer.
- Co-chair and organizer, Experimental Biology-Feature Topic: pH Homeostasis and Acid-Base Transport, 2019.
- Organizer, National Institute of Diabetes and Digestive and Kidney Diseases Division of Kidney, Urologic, and Hematologic Diseases Summer Undergraduate Research Symposium, Mayo Clinic, 2016.
- Chair and organizer, BioMedical Transporters conference: "Structure of Transporters," Berne, Switzerland, 2007.
- Presidential Discovery Award, Mayo Clinic, 2019.
- Vice chair, Cell and Molecular Section, American Physiology Society, 2006-2012.
- Tenure, Case Western Reserve University School of Medicine, 2006.