Breaking News
February 16, 2019 - Neuroscientists show how the brain responds to texture
February 16, 2019 - Gilead Announces Topline Data From Phase 3 STELLAR-4 Study of Selonsertib in Compensated Cirrhosis (F4) Due to Nonalcoholic Steatohepatitis (NASH)
February 16, 2019 - What Can I Do About Sweating? (for Teens)
February 16, 2019 - Companies navigate dementia conversations with older workers
February 16, 2019 - Newly developed stem cell technologies show promise for treating PD patients
February 16, 2019 - Collaborative material research could advance self-assembling nanomaterials
February 16, 2019 - Researchers take major step in creating technology that mimics the human brain
February 16, 2019 - Erasing memories associated with cocaine use reduces drug seeking behavior
February 16, 2019 - Artificial intelligence can accurately predict prognosis of ovarian cancer patients
February 16, 2019 - Racial disparities in cancer deaths on the decline for America
February 16, 2019 - FDA authorizes new interoperable insulin pump for children, adults with diabetes
February 16, 2019 - Coexisting Medical Conditions, Smoking Explain PTSD-CVD Link
February 16, 2019 - Skin Cancer Screening: MedlinePlus Lab Test Information
February 16, 2019 - ‘Happiness’ exercises can boost mood in those recovering from substance use disorder
February 16, 2019 - Cell manipulation could soon halt or reverse aging
February 16, 2019 - Pumped Breast Milk Falls Short of Breastfed Version
February 16, 2019 - Men’s porn habits could fuel partners’ eating disorders, study suggests
February 16, 2019 - Rapid progression of age-related diseases may result from formation of vicious cycles
February 16, 2019 - Immune checkpoint molecule protects against future development of cancer
February 16, 2019 - New method produces hydrogels that have properties similar to cells’ environment
February 16, 2019 - $4.1 million funding for heart research on Valentine’s Day
February 16, 2019 - General anesthesia in early infancy unlikely to have lasting effects on developing brains
February 16, 2019 - New breakthroughs for muscular dystrophy research
February 16, 2019 - First Opinion: Embryo editing for higher IQ is a fantasy. Embryo profiling for it is almost here
February 16, 2019 - Vapers develop cancer-related gene deregulation as cigarette smokers
February 16, 2019 - Bringing Antimicrobial Susceptibility Testing (AST) to the Community
February 16, 2019 - Decolonization protocol after hospital discharge can prevent dangerous infections
February 16, 2019 - H-RT should be the standard of care for men with low risk prostate cancer, study shows
February 16, 2019 - New technique using patients’ own modified cells could help treat Crohn’s disease
February 16, 2019 - Therapeutic endoscopy has an expanding role in the treatment of IBD
February 16, 2019 - Blood clot discovery could lead to development of better treatments for blood diseases
February 16, 2019 - Intervention can increase exclusive breastfeeding rates
February 16, 2019 - New project explores how gaming technologies can help cancer patients communicate better
February 16, 2019 - Catalyst Biosciences Presents Updated Data from Its Phase 2/3 Trial of Subcutaneous Marzeptacog Alfa (Activated) in Individuals with Hemophilia A or B with Inhibitors at the 12th Annual EAHAD Congress
February 16, 2019 - Rerouting nerves during amputation reduces phantom limb pain before it starts
February 16, 2019 - A Hormone Produced When We Exercise Might Help Fight Alzheimer’s
February 16, 2019 - Millions of British people breathe toxic air travelling to GPs
February 16, 2019 - Conformance of genetic characteristics found to be crucial for longer preservation of kidney graft
February 16, 2019 - Researchers use optogenetic tool to control, visualize receptor signals in neural cells
February 16, 2019 - New reversible antiplatelet therapy could reduce risk of blood clots, prevent cancer metastasis
February 16, 2019 - Testosterone is not the only hormone needed for penis development
February 16, 2019 - FDA Advisory Committee Recommends Approval of Spravato (esketamine) Nasal Spray for Adults with Treatment-Resistant Depression
February 15, 2019 - Heart surgery technology developed at Baptist Health debuts after years of secrecy
February 15, 2019 - Prescription Opioids Double Risk of Triggering Fatal Car Crash
February 15, 2019 - New study helps doctors better understand high blood pressure in pregnant women
February 15, 2019 - Beta wave control in Parkinson’s diseased brain could be a potential therapy
February 15, 2019 - Media representations of love may justify gender-based violence in young people
February 15, 2019 - Yoga May Help With Rheumatoid Arthritis Symptoms, Severity
February 15, 2019 - Obstructive sleep apnea linked to inflammation, organ dysfunction
February 15, 2019 - Master your mind: A challenge from WELL for Life
February 15, 2019 - Why Some Brain Tumors Respond to Immunotherapy
February 15, 2019 - Must-Reads Of The Week From Brianna Labuskes
February 15, 2019 - Researchers uncover novel mechanism and potential new therapeutic target for Alzheimer’s
February 15, 2019 - Genetic variations in a fourth gene associated with higher ALL risk in Hispanic children
February 15, 2019 - Disruptive behavioral problems in kindergarten linked with lower employment earnings in adulthood
February 15, 2019 - New bioengineered device enhances the production of T-cells
February 15, 2019 - HDL proteome behaves like a tiny Velcro ball that is rolling on surfaces
February 15, 2019 - Puerto Rican children more likely to have poor or decreasing use of asthma inhalers
February 15, 2019 - Quality of patient care does not improve after physician-hospital integration
February 15, 2019 - Synopsys release new software for implant design and patient-specific planning
February 15, 2019 - 6 out of 10 hip replacements last 25 years or longer
February 15, 2019 - Health Tip: What You Should Know About Antibiotics
February 15, 2019 - New research challenges medical consensus that adenoids and tonsils significantly shrink during teenage years
February 15, 2019 - Discovery of weakness in a rare cancer could be exploited with drugs
February 15, 2019 - UVA scientists find potential explanation for mysterious cell death in Alzheimer’s, Parkinson’s
February 15, 2019 - New rules requiring female athletes to lower testosterone levels are based on flawed data
February 15, 2019 - Researchers comprehensively sequence the human immune system
February 15, 2019 - Researchers study animal venoms to identify new medicines for treating diseases
February 15, 2019 - Movement of wrist bones revealed by MRI and computer modeling
February 15, 2019 - Philips introduces new premium digital X-ray room to help shorten patient wait times
February 15, 2019 - Women fare worse than men following aortic heart surgery, study finds
February 15, 2019 - High-protein and low-calorie diet helps older adults lose weight safely, shows study
February 15, 2019 - Drug microdosing effects may not measure up to big expectations
February 15, 2019 - Discharged, Dismissed: ERs Often Miss Chance To Set Overdose Survivors On ‘Better Path’
February 15, 2019 - A digitized lab environment to be showcased at smartLAB 2019
February 15, 2019 - Scientists uncover main mechanisms of fluconazole drug resistance
February 15, 2019 - New study seeks to understand how colibactin causes cancer
February 15, 2019 - Photoacoustic imaging accurately measures the temperature of deep tissues
February 15, 2019 - Large study finds no association between phthalate exposure and breast cancer risk
February 15, 2019 - New research explains presence of ‘natural’ magnetism in human cells
Carnegie scientist awarded NIH grant to identify novel medicines for cardiovascular disease

Carnegie scientist awarded NIH grant to identify novel medicines for cardiovascular disease

image_pdfDownload PDFimage_print

Carnegie’s Department of Embryology scientist Steven Farber and team have been awarded a 5-year $3.3-million NIH grant to identify novel pharmaceuticals for combatting a host of diseases associated with altered levels of lipoproteins like LDL (“bad cholesterol”). Obesity, diabetes, cardiovascular disease, fatty liver disease, and metabolic syndrome have all been linked to changes in plasma lipoproteins.

Lab efforts, led by graduate student Jay Thierer, started by creating zebrafish that have been genetically engineered to produce glowing lipoproteins, a technique they call “LipoGlo”. This was achieved by attaching DNA encoding NanoLuc (a relative of the protein that makes fireflies glow) to Apolipoprotein-B (ApoB), the protein that carries bad cholesterol. Since all the types of lipoprotein particles that are thought to actually cause cardiovascular disease are made with one copy of the ApoB protein, the team just needs to quantify the amount of light coming from the fish and they know exactly how many disease causing particles there are. Finding compounds that lower ApoB levels could be an enormous boost to fighting cardiovascular disease.

To identify such compounds, Farber teamed up with Johns Hopkins Researchers Rexford Ahima, Thomas Lectka, and Jeffery Mumm and proposed a high-throughput screen that tests thousands of small molecules in live zebrafish larvae to identify those that lower ApoB. In addition, they developed a collection of secondary screens to help them figure out how a given compound achieves its ApoB-lowering effect.

What sets this research apart is its ability to study cardiovascular disease in the context of a living organism. Previous attempts to develop cardiovascular disease drugs have almost exclusively relied on studying a single cell type, such as finding ways to prevent liver cells from producing cholesterol. However, it is remarkably difficult to predict how changes in one cell type will affect the rest of the organism, as many tissues including muscle, fat, blood vessels, the liver, the intestine, and the brain all interact and communicate to regulate cholesterol.

What has made this effort possible are the unique attributes of the larval zebrafish system. Zebrafish have almost all of the major components of human metabolism, but in a small, rapidly developing organism that can be moved around and placed in tiny wells with robots. In a single week, the team can raise over 20,000 larvae and test hundreds of compounds, something that might take months or years in other vertebrate animal systems. Additionally, larvae are translucent which enables the team to monitor a host of other aspects of metabolic health such as fat accumulation and inflammation using other genetically engineered fish with “glowing” markers of biological processes. Mumm’s lab pioneered the zebrafish robotic platform for studies of eye biology and brought that expertise to the team. Lectka’s expertise in small molecule chemistry will assist in selecting the most promising compounds that could most easily be transformed into drugs for humans. These carefully selected candidate drugs will be handed off to the Ahima lab to test their efficacy in mouse models of obesity and cardiovascular disease.

Farber pointed out that “25% of the world’s population dies of cardiovascular disease. While statin drugs have had a major impact on reducing mortality, folks still die from cardiovascular disease.” He went on to explain that although ApoB has a well-known role in metabolic disease, this protein is “enormous,” making it nearly impossible to study using traditional molecular techniques. By embracing state-of-the-art genome engineering approaches, Farber and his team were able to overcome this issue and generate zebrafish with glowing lipoproteins.

Farber remarked: “While most of the field works in humans or mouse, my lab pioneered the use of zebrafish for studies of lipid metabolism. What we proposed is simply not possible in any other vertebrate model system. I will never forget the day Jay walked into my office and showed me images of larval zebrafish revealing the locations of all of the ApoB containing lipoproteins…just so cool.”

Source:

https://carnegiescience.edu/news/steven-farber-awarded-33-million-nih-grant-identify-new-pharmaceuticals-fight-cardiovascular

Tagged with:

About author

Related Articles