Breaking News
December 12, 2018 - Study provides new information regarding microRNA function in cellular homeostasis of zebrafish
December 12, 2018 - Study provides new understanding of mysterious ‘hereditary swelling’
December 12, 2018 - Researchers shed new light on how to combat Shiga and ricin toxins
December 12, 2018 - Pregnant Women Commonly Refuse Vaccines
December 12, 2018 - Drug treatment could offer new hope for some patients with brain bleeding
December 12, 2018 - Health care financial burden of animal-related injuries is growing, study says
December 12, 2018 - Macrophage cells could help repair the heart following a heart attack, study finds
December 12, 2018 - Researchers develop new system for efficiently producing human norovirus
December 12, 2018 - New artificial intelligence-based system to differentiate between different types of cancer cells
December 11, 2018 - Healthy Lifestyle Lowers Odds of Breast Cancer’s Return
December 11, 2018 - New research identifies two genes linked to serious congenital heart condition
December 11, 2018 - NIH Director talks science, STEM careers with preteens
December 11, 2018 - Disabling a Cellular Antivirus System Could Improve Gene Therapy
December 11, 2018 - New tool swiftly provides accurate measure of patients’ cognitive difficulties
December 11, 2018 - NICE releases new guidelines for diagnosis and management of COPD
December 11, 2018 - Without Obamacare penalty, think it’ll be nice to drop your plan? Better think twice
December 11, 2018 - Researchers capture high-resolution X-ray and NMR image of key immune regulator
December 11, 2018 - Natural flavonoid is effective at treating leishmanisis infections, study shows
December 11, 2018 - Avoidant grievers unconsciously monitor and block mind-wandering contents, study shows
December 11, 2018 - Study identifies how hantaviruses infect lung cells
December 11, 2018 - Improving PTSD care through genetics
December 11, 2018 - Dermatology providers show interest in recommending cannabinoids to patients
December 11, 2018 - Researchers to study effects of electroconvulsive therapy on Alzheimer’s patients with aggression
December 11, 2018 - Four dried fruits have lower glycemic index than starchy foods, study finds
December 11, 2018 - Optimization of drug dose sizes can reduce pharmaceutical wastage
December 11, 2018 - Ultrarestrictive opioid prescribing strategy linked with reduction in number of pills dispensed
December 11, 2018 - PET scans to optimize tuberculosis meningitis treatments and personalize care, study finds
December 11, 2018 - Researchers aim to identify and target high blood pressure indicators
December 11, 2018 - Researchers identify immune cell subset that may drive chronic inflammation
December 11, 2018 - Ezogabine treatment reduces motor neuron excitability in ALS patients, study shows
December 11, 2018 - One implant, two prices. It depends on who’s paying.
December 11, 2018 - Standardizing feeding practices improves growth trends for micro-preemies
December 11, 2018 - COPD Tied to Obesity in Male, Female Never-Smokers
December 11, 2018 - Flossing: Information for Caregivers
December 11, 2018 - Does breastfeeding hormone protect against type 2 diabetes?
December 11, 2018 - Educating future doctors to prescribe physical activity for their patients
December 11, 2018 - Krystal 2000 microplate design improves fluorescence and luminescence measurement
December 11, 2018 - FDA clears mobile medical app to help increase retention in recovery program for opioid use disorder
December 11, 2018 - Overcoming Challenges in High-Speed Centrifugation Experiments
December 11, 2018 - Study shows link between neighborhoods’ socioeconomic status and dietary choices
December 11, 2018 - Lower BMI before obesity surgery predicts greater post-operative weight loss, study finds
December 11, 2018 - Obesity May Be Driving Rise in Uterine Cancers
December 11, 2018 - Antioxidants may prevent cognitive impairment in diabetes
December 11, 2018 - Study discovers link between meditation and how individuals respond to feedback
December 11, 2018 - Researchers identify potential diagnostic tool for Alzheimer’s disease
December 11, 2018 - Oral cancer prognostic signature identified
December 11, 2018 - How Can I Find Out What Caused My Miscarriage?
December 11, 2018 - Novel personalized medicine tool for assessing inherited colorectal cancer syndrome risk developed
December 11, 2018 - Study uncovers 11 new genes associated with epilepsy
December 11, 2018 - Filling research gaps could help develop more disability-inclusive workplaces
December 11, 2018 - Cartilage tissue engineering brings good news for patients with cartilage defects
December 11, 2018 - Novel 3D printing workflow helps predict leaky heart valves
December 11, 2018 - Imagination can help overcome fear and anxiety-related disorders, shows study
December 11, 2018 - Are caries linked to political regime?
December 11, 2018 - Leader in Diabetes Clinical Trials Wins Naomi Berrie Award
December 11, 2018 - Scientists discover cellular mechanism that triggers pneumonia in humans
December 11, 2018 - Increasing mental health problems related to drug use in over 55’s
December 11, 2018 - High-intensity interval exercise could help combat cognitive dysfunction in obese people
December 11, 2018 - Annual flu shot can save lives of heart failure patients
December 11, 2018 - Researchers compare health outcomes for VA and non-VA hospitals
December 11, 2018 - Recommendations Developed for Psoriatic Arthritis Treatment
December 11, 2018 - Genetic analysis links obesity with diabetes, coronary artery disease
December 11, 2018 - Study shows that having genetic information can affect how the body responds
December 11, 2018 - UNAIDS Report: 9 Million Are Likely HIV Positive And Don't Know It
December 11, 2018 - Lund University researchers succeed in obtaining dendritic cells by direct reprogramming
December 11, 2018 - Breast tumors recruit bone marrow cells to boost their growth, study reveals
December 11, 2018 - Updated breast cancer screening guideline highlights importance of shared decision-making
December 11, 2018 - EHR-related stress associated with physician burnout
December 11, 2018 - AHA: 12-Year-Old Heart Defect Survivor Inspires NFL Player’s Foundation
December 11, 2018 - Breast cancer patients who take heart drug with trastuzumab have less heart damage
December 11, 2018 - Providing aid to those humans – and animals – affected by the California fires
December 11, 2018 - Even without proof, CBD is finding a niche as a cure-all
December 11, 2018 - Drawing leads to better memory than writing
December 11, 2018 - Researchers report novel findings on plant hormone
December 10, 2018 - A Tale of Two Labels
December 10, 2018 - Triple combination cancer immunotherapy improves outcomes in preclinical melanoma model
December 10, 2018 - A 14-year-old explains what it’s like to get a new heart
December 10, 2018 - Team Players Honored with 2018 Baton Awards
December 10, 2018 - Global report highlights how the changing world is affecting children’s physical activity levels
December 10, 2018 - Genes play a role in physical activity and sleep
CWRH/UH researcher receives grant to study role of KLF2 factor in vascular-related disorders

CWRH/UH researcher receives grant to study role of KLF2 factor in vascular-related disorders

image_pdfDownload PDFimage_print

Transcription factors are proteins that determine whether specific genes are transcribed or not by binding to DNA. In other words, they help turn genes “on” or “off.”

One such transcription factor, Kruppel-like factor (KLF) 2, plays a central role in many processes critical to cardiovascular homeostasis. Researchers also understand that levels of KLF2 increase with health and decline with disease. “We are very keen to identify the cellular pathways that regulate the increase or decrease in KLF2 levels in order to develop novel strategies to sustain levels and ameliorate cardiovascular disorders,” said Mukesh K. Jain, MD, professor of medicine at Case Western Reserve University School of Medicine and the Ellery Sedgwick Jr. Chair & Distinguished Scientist, University Hospitals Cleveland Medical Center. He is part of a trans-Atlantic network of international leaders in cardiovascular medicine who aim to find out.

Jain and his colleagues have been awarded a five-year, $6M grant from the Paris-based Fondation Leducq to conduct a thorough analysis of the pivotal role of KLF2 in vascular-related functions and disorders. The team’s grant was one of five awarded globally and is, in the French foundation’s words, “an indication of [our] enthusiasm for your proposal, and faith that the collaborative work of the network will significantly improve our knowledge and treatment of cardiovascular disease.”

Joining Jain as part of the research team are eminent researchers from Yale University, the University of Oxford, the University of Pennsylvania, and the Max Planck Institute for Molecular Biomedicine in Germany.

KLF2 and members of this family of transcription factors regulate hundreds of genes that control blood vessel function, often simultaneously, turning on and standardizing a coordinated genetic program governing vascular health. This includes the development of new blood vessels in embryos and adults and embryonic heart valve formation. KLF2 is also a major anti-inflammatory and anti-clotting agent, thereby promoting vascular health. But lower levels of KLF2 can cause inflammation and narrowing of the arteries, resulting in blockages in blood vessels, conditions that affect tens of millions of people worldwide. Additionally, the effects of cardiac medicines known as statins are mediated in part through KLFs.

How is KLF2 involved in such a broad range of life-sustaining activities and potentially lethal breakdowns?

To help answer this question, Jain and his colleagues have three aims. First, determine how KLF2 actually functions within a cell. This entails illuminating the cellular machinery it uses in controlling vascular processes. Second, determine what specific genes with blood vessels it targets to turn on and off. Third, test the findings of aims one and two in both human tissues and relevant mouse genetic models. The team expects that these studies will reveal the full KLF2 regulatory set of connections and identify new treatment targets for cardiovascular disease. The team will use insights from its studies on KLF2 to conduct analysis of KLF4, a related molecule with similar functions.

“KLFs are now known to serve as master regulators of the endothelium, the tissue that forms a single layer of cells lining the blood vessels, heart, and lymphatic vessels,” said Jain. “Studying the mechanisms of KLF2 expression and its involvement in vascular physiology, and gaining an ability to control that function, have the potential to treat a broad array of cardiovascular diseases ranging from stroke and heart attack to brain-based cerebrovascular malformations.”

Among its techniques, the research team will use CRISPR-Cas9-based approaches to delete certain genes in the KLF2 sequencing process and determine what affect this has on vascular development and function. This will help specify which genes are involved in various processes and diseases, boosting overall understanding and identifying targets for treatment, either through medication or gene-editing. The researchers will also utilize already FDA-approved medications on human cells and mice, seeking to determine which ones might be used to target the findings of the investigative team.

This work builds on seminal findings Jain published in 2004 that led to the discovery of KLFs in vascular biology. While KLFs were known to regulate critical functions based on studies in the 1970’s and 1980’s in flies, the link to cardinal functions of blood vessels was amongst the first in mammalian systems and represented a major advance in cardiovascular biology. KLFs have also been implicated in numerous biological processes that affect the development of cancer, metabolic disorders, immune dysfunction, and aging.​

Source:

http://casemed.case.edu/cwrumed360/news-releases/release.cfm?news_id=1548&news_category=8

Tagged with:

About author

Related Articles