More than than 30% of Americans are at risk of kidney disease, and nearly 20% of all Medicare spending is for kidney disease in patients 65 and older. Yet there is still much not known about the development of kidney disease.
Dr. Indra Chandrasekarand her team of researchers recently published an article in the biomedical research journal JCI Insight, highlighting the impact of key cellular processes on kidney health and function. The discovery allows researchers to better understand how kidney disease forms.
The kidney carries out many functions that are necessary to maintain overall health. As a result, any disruption to those functions can cause kidney disease. To find where kidney disease starts, the Chandrasekar Lab chose to study functions at the cellular level.
When researchers turned off the genes for certain proteins in mice at 4 weeks of age, the mice began to exhibit worsening dilation of the kidney tubules accompanied by eventual kidney degeneration and cyst formation by 12 weeks of age. Along with these structural changes came functional changes within the kidneys, including more acidic urine, excretion of protein and salts, and inflammation as the disease progressed.
This work highlights a new and major role for the proteins, called nonmuscle myosin II (NM2A and NM2B), in maintaining the health and function of the kidneys. This finding provides key knowledge to the kidney disease field as the pursuit of a cure continues to drive the valuable work being performed at Sanford Research.
Dr. Indra Chandrasekar sat down to talk with Sanford Health News about her history with Sanford Research and her recent work.
The myosin motor family, and NM2 proteins in particular, has been studied for over five decades. NM2s role in cell migration, adhesion and cell division has been carefully examined in vitro as well as with organismal and developmental context. Work in the Chandrasekar Lab is focused on understanding the physiological and cell-type specific role for NM2 mediated cellular transport mechanisms using mouse kidney as a model. Turning off the NM2 genes in adult mouse kidney tubular epithelial cells demonstrates that NM2 function is critical for the transport of two important proteins within kidney. These two proteins are called uromodulin (UMOD) and sodium, potassium, chloride cotransporter (NKCC2), that are essential for maintaining electrolyte balance and blood pressure in our body.
Mutations in UMOD and NKCC2 genes in humans lead to kidney disease. Membrane-associated NKCC2 has been the target of several blood-pressure regulating medicines currently on the market. Therefore, it is critical to further explore and understand how NM2 proteins regulate UMOD and NKCC2 transport and function in within the kidney cells.
Personally, this published work has been our teams mission for the past several years. As the Nobel-prize winning neurobiologist Rita Levi-Montalcini once said, I dont believe there would be any science at all without intuition. The findings described in this manuscript began as an intuition that stemmed from my postdoctoral work. I am very happy with how it turned out and extremely grateful for our teams hard work.
As a cell biologist, I am fascinated by the molecular and cellular complexity of the kidney. Considering that mutations in MYH9 (NM2A protein) in humans are linked to kidney disease, and that the epithelial cells of the kidney are great models to study cellular transport pathways, it was an easy organ of choice. Moreover, the availability of excellent mouse genetic tools to perform cell-type specific, inducible and conditional gene inactivation in the kidney is also a positive.
The impact of our published work is twofold:
I worked at a local clinical laboratory in town during the first year of my undergraduate biochemistry program. My job was to prepare, stain and perform microscopic analysis of peripheral blood smears from patient blood. I was fascinated by the cellular morphology, staining characteristics and intracellular organelles present in the varying types of blood cells. I wanted to understand how different cell types in our body function and what happens when they do not perform their assigned jobs. This interest led me to Dr. Brigitte M. Jockushs laboratory in Germany for my Graduate work. Professor Jockusch is a well-respected expert in the field of cytoskeletal research and cell biology. Being in her lab was a great privilege. I continued my training with prominent cell biologists such as Dr. John A. Cooper and Dr. Paul C. Bridgman at the Washington University in St. Louis.
During my training as a post-doctoral scientist at Washington University in St. Louis, I had determined a new, critical role for nonmuscle myosin 2 (NM2) motors in processes by which proteins are transported into and within cells. At Sanford Research, I got the opportunity to follow on my previous findings and to start an independent research program to understand the molecular mechanisms underlying kidney tubular transport defects to human kidney diseases. The excellent, state-of-the-art facilities to conduct basic and clinical research at Sanford Research has led us to publish a manuscript of high impact that reports that the loss of NM2 proteins in adult kidney epithelium results in progressive chronic kidney disease.
I enjoy thinking about new ideas and concepts and testing those using experiments in the lab to gain insights into cellular mechanisms. I love performing advanced microscopy experiments. However, the most enjoyment comes from passing along the valuable techniques and scientific concepts to future scientists who are trainees and let them excel in whatever they desire in their life.
Posted In Genetics, Health Care Heroes, Research
Excerpt from:
A clue to the causes of kidney disease: It's in your cells - Sanford Health News
- Bristol researcher awarded Women in Cell Biology Early Career Medal 2025 - University of Bristol - December 23rd, 2024 [December 23rd, 2024]
- Simple and effective embedding model for single-cell biology built from ChatGPT - Nature.com - December 9th, 2024 [December 9th, 2024]
- Distinguished investigator brings expertise in genetics and cell biology to Texas A&M AgriLife - AgriLife Today - October 26th, 2024 [October 26th, 2024]
- Institute of Molecular and Cell Biology (IMCB) - Agency for Science, Technology and Research (A*STAR) - October 13th, 2024 [October 13th, 2024]
- Joseph Gall, father of modern cell biology, dead at 96 - Carnegie Institution for Science - September 15th, 2024 [September 15th, 2024]
- A dual role of ERGIC-localized Rabs in TMED10-mediated unconventional protein secretion - Nature.com - June 27th, 2024 [June 27th, 2024]
- Yoshihiro Yoneda Appointed President of the International Human Frontier Science Program Organization - PR Newswire - June 27th, 2024 [June 27th, 2024]
- A new way to measure ageing and disease risk with the protein aggregation clock - EurekAlert - June 18th, 2024 [June 18th, 2024]
- How Flow Cytometry Spurred Cell Biology - The Scientist - June 18th, 2024 [June 18th, 2024]
- Building Cells from the Bottom Up - The Scientist - June 18th, 2024 [June 18th, 2024]
- From Code to Creature - The Scientist - June 18th, 2024 [June 18th, 2024]
- Adding intrinsically disordered proteins to biological ageing clocks - Nature.com - May 24th, 2024 [May 24th, 2024]
- Advancing Cell Biology and Cancer Research via Cell Culture and Microscopy Imaging Techniques - Lab Manager Magazine - May 24th, 2024 [May 24th, 2024]
- Study explores how different modes of cell division evolved in close relatives of fungi and animals - News-Medical.Net - May 24th, 2024 [May 24th, 2024]
- Solving the Wnt nuclear puzzle - Nature.com - May 24th, 2024 [May 24th, 2024]
- Prof. Jay Shendure Joins Somite Therapeutics as Scientific Co-founder - BioSpace - May 24th, 2024 [May 24th, 2024]
- One essential step for a germ cell, one giant leap for the future of reproductive medicine - EurekAlert - May 24th, 2024 [May 24th, 2024]
- May: academy-medical-sciences | News and features - University of Bristol - May 24th, 2024 [May 24th, 2024]
- Universal tool for tracking cell-to-cell interactions - ASBMB Today - May 24th, 2024 [May 24th, 2024]
- Close Encounters of Skin and Nerve Cells - The Scientist - April 15th, 2024 [April 15th, 2024]
- OrthoID: Decoding Cellular Conversations with Cutting-Edge Technology - yTech - April 15th, 2024 [April 15th, 2024]
- Impact of aldehydes on DNA damage and aging - EurekAlert - April 15th, 2024 [April 15th, 2024]
- Redefining Cell Biology: Nondestructive Genetic Insights With Raman Spectroscopy - SciTechDaily - March 29th, 2024 [March 29th, 2024]
- Scientists Unravel the Unusual Cell Biology Behind Toxic Algal Blooms - SciTechDaily - March 19th, 2024 [March 19th, 2024]
- Ancient retroviruses played a key role in the evolution of vertebrate brains - EurekAlert - February 21st, 2024 [February 21st, 2024]
- Singapore scientists uncover a crucial link between cholesterol synthesis and cancer progression - EurekAlert - February 4th, 2024 [February 4th, 2024]
- Scientists uncover a way to "hack" neurons' internal clocks to speed up brain cell development - News-Medical.Net - February 4th, 2024 [February 4th, 2024]
- First atomic-scale 'movie' of microtubules under construction, a key process for cell division - EurekAlert - February 4th, 2024 [February 4th, 2024]
- Small RNAs take on the big task of helping skin wounds heal better and faster with minimal scarring - EurekAlert - February 4th, 2024 [February 4th, 2024]
- Shengjie Feng channels the powers of cryogenic electron microscopy - Newswise - January 19th, 2024 [January 19th, 2024]
- Study pinpoints breast cancer cells-of-origi - EurekAlert - January 19th, 2024 [January 19th, 2024]
- New analysis of cancer cells identifies 370 targets for smarter, personalized treatments - News-Medical.Net - January 19th, 2024 [January 19th, 2024]
- EU funding for pioneering research on the treatment of gliomas - EurekAlert - January 19th, 2024 [January 19th, 2024]
- The future of mRNA biology and AI convergence - Drug Target Review - December 22nd, 2023 [December 22nd, 2023]
- The future of artificial breast milk, according to one lab - Quartz - December 22nd, 2023 [December 22nd, 2023]
- Shedding new light on the hidden organization of the cytoplasm - News-Medical.Net - December 22nd, 2023 [December 22nd, 2023]
- Bugs that help bugs: How environmental microbes boost fruit fly reproduction - EurekAlert - December 22nd, 2023 [December 22nd, 2023]
- Cells Move in Groups Differently Than They Do When Alone - NYU Langone Health - December 14th, 2023 [December 14th, 2023]
- Cells move in groups differently than they do when alone - EurekAlert - December 14th, 2023 [December 14th, 2023]
- Seattle Hub for Synthetic Biology plans to transform cells into tiny recording devices - GeekWire - December 14th, 2023 [December 14th, 2023]
- Virginia Tech and Weizmann Institute of Science tackle cell ... - Virginia Tech - October 16th, 2023 [October 16th, 2023]
- Vast diversity of human brain cell types revealed in trove of new ... - Spectrum - Autism Research News - October 16th, 2023 [October 16th, 2023]
- Singamaneni to develop advanced protein imaging method - The ... - Washington University in St. Louis - October 16th, 2023 [October 16th, 2023]
- Researchers find certain cancers can activate 'enhancer' in the ... - University of Toronto - October 16th, 2023 [October 16th, 2023]
- 2023 Hettleman Prizes awarded to five exceptional early-career ... - UNC Research - October 16th, 2023 [October 16th, 2023]
- Faeth Therapeutics Announces National Academy of Medicine ... - BioSpace - October 16th, 2023 [October 16th, 2023]
- From Migrant Farm Worker to Duke Scientist, Everardo Macias ... - Duke University School of Medicine - October 16th, 2023 [October 16th, 2023]
- Finding the golden ticket? Cyclin T1 is required for HIV-1 latency ... - Fred Hutch News Service - October 16th, 2023 [October 16th, 2023]
- Spermidine May Improve Egg Health and Fertility - Lifespan.io News - October 16th, 2023 [October 16th, 2023]
- Molecule discovered that grows bigger and stronger muscles - Earth.com - October 16th, 2023 [October 16th, 2023]
- SGIOY: 3 Biotech Stocks With Potential Future Gains - StockNews.com - October 16th, 2023 [October 16th, 2023]
- Association for Molecular Pathology Publishes Best Practice ... - Technology Networks - October 16th, 2023 [October 16th, 2023]
- A new cell type with links to gastric cancer steps up for its mugshot - Fred Hutch News Service - October 16th, 2023 [October 16th, 2023]
- Programmed cell death may be 1.8 billion year - EurekAlert - October 16th, 2023 [October 16th, 2023]
- New study confirms presence of flesh-eating and illness-causing ... - Science Daily - October 16th, 2023 [October 16th, 2023]
- New Institute for Immunologic Intervention (3i) at the Hackensack ... - Hackensack Meridian Health - October 16th, 2023 [October 16th, 2023]
- Post-doctoral Fellow in Cancer Biology in the Department of ... - Times Higher Education - October 16th, 2023 [October 16th, 2023]
- Scientists uncover key enzymes involved in bacterial pathogenicity - News-Medical.Net - October 16th, 2023 [October 16th, 2023]
- B cell response after influenza vaccine in young and older adults - EurekAlert - October 16th, 2023 [October 16th, 2023]
- Post-doctoral researcher in yeast cell biology job with UNIVERSITY ... - Times Higher Education - April 8th, 2023 [April 8th, 2023]
- expert reaction to study looking at creating embryo-like structures ... - Science Media Centre - April 8th, 2023 [April 8th, 2023]
- UCF Bone Researcher Receives National Recognition - UCF - April 8th, 2023 [April 8th, 2023]
- PhenomeX to Participate in American Association of Cancer ... - BioSpace - April 8th, 2023 [April 8th, 2023]
- Inland Empire stem-cell therapy gets $2.9 million booster - UC Riverside - April 8th, 2023 [April 8th, 2023]
- New finding in roundworms upends classical thinking about animal cell differentiation - News-Medical.Net - April 8th, 2023 [April 8th, 2023]
- Biology's unsolved chicken-or-egg problem: Where did life come from? - Big Think - April 8th, 2023 [April 8th, 2023]
- Azacitidine in Combination With Trametinib May Be Effective for ... - The ASCO Post - April 8th, 2023 [April 8th, 2023]
- Researchers clear the way for well-rounded view of cellular defects - Phys.org - April 8th, 2023 [April 8th, 2023]
- We were dancing around the lab cellular identity discovery has potential to impact cancer treatments - Newswise - April 8th, 2023 [April 8th, 2023]
- Environmental stressors' effect on gene expression explored in lecture - Environmental Factor Newsletter - April 8th, 2023 [April 8th, 2023]
- RNA therapy restores gene function in monkeys modeling ... - Spectrum - Autism Research News - April 8th, 2023 [April 8th, 2023]
- Traumatic brain injury interferes with immune system cells' recycling ... - Science Daily - April 8th, 2023 [April 8th, 2023]
- Lab-grown fat could give cultured meat real flavor and texture - EurekAlert - April 8th, 2023 [April 8th, 2023]
- Researchers reveal mechanism of polarized cortex assembly in migrating cells - Phys.org - April 8th, 2023 [April 8th, 2023]
- Probing Selfish Centromeres Unveils an Evolutionary Arms Race - The Scientist - April 8th, 2023 [April 8th, 2023]
- Meet the 2023 Outstanding Graduating Students - UMaine News ... - University of Maine - April 8th, 2023 [April 8th, 2023]
- The Worlds Sexiest Fragrance Unveiled, But Its Not For You - Revyuh - April 8th, 2023 [April 8th, 2023]
- City of Hope appoints John D. Carpten, Ph.D., as director of its ... - BioSpace - April 8th, 2023 [April 8th, 2023]
- Modernized Algorithm Predicts Drug Targets for SARS-CoV-2, Other ... - GenomeWeb - April 8th, 2023 [April 8th, 2023]
- BU researcher wins $3.9 million NIH grant to develop novel therapeutic modalities for Alzheimer's - News-Medical.Net - April 8th, 2023 [April 8th, 2023]