Mary R Stahley studies how to use a powerful gene-editing tool called CRISPR to modify genes that regulate cholesterol levels in the body. Specifically, her research targets a gene known as PCSK9, which influences how cholesterol is produced in the liver. By using CRISPR, she aims to create lasting changes that could help people at risk for heart disease, potentially allowing them to bypass the need for ongoing cholesterol-lowering medications. Her techniques involve delivering the gene-editing tools through small fat particles directly into patients' bloodstream, showcasing an innovative approach to treating high cholesterol.
Key findings
A single CRISPR treatment led to a 60% reduction in cholesterol levels in primates.
The cholesterol-lowering effect lasted for at least 8 months without additional treatment.
This research opens the door for a one-time gene therapy solution for patients instead of lifelong cholesterol drugs.
Frequently asked questions
Does Dr. Stahley study cholesterol levels?
Yes, Dr. Stahley's research specifically focuses on lowering cholesterol through gene editing.
What treatments has Dr. Stahley researched?
She has researched the use of CRISPR gene editing to address high cholesterol by targeting the PCSK9 gene.
Is Dr. Stahley's work relevant to heart disease patients?
Absolutely, her research has the potential to provide heart disease patients with a long-lasting treatment for high cholesterol.
Publications in plain English
In vivo CRISPR base editing of PCSK9 durably lowers cholesterol in primates.
2021
Nature
Musunuru K, Chadwick AC, Mizoguchi T, Garcia SP, DeNizio JE +37 more
Plain English Researchers used a gene-editing tool called CRISPR to permanently disable a gene in monkeys' livers that controls cholesterol production, delivering it through tiny fat particles injected into the bloodstream. After a single injection, the monkeys' cholesterol dropped by about 60% and stayed low for at least 8 months without any additional treatment. This proves that gene editing could offer heart disease patients a one-time treatment instead of taking cholesterol drugs for life.
Plain English This study examined ways to enhance mRNA therapies, which are becoming important for treating various diseases. Researchers found that by designing proteins more effectively, they could increase their activity and duration in living organisms. For instance, their methods led to improved protein performance in laboratory tests and confirmed these benefits in mice, which is important because it could lead to longer-lasting and more effective treatments for conditions that require repeated mRNA doses.
Who this helps: This research benefits patients undergoing mRNA treatment for diseases like metabolic disorders.
Optimization of mRNA untranslated regions for improved expression of therapeutic mRNA.
2018
RNA biology
Asrani KH, Farelli JD, Stahley MR, Miller RL, Cheng CJ +2 more
Plain English This study focused on improving the effectiveness of mRNA therapies by modifying specific parts of the mRNA called untranslated regions (UTRs) to enhance the production of a protein called Arginase 1 (ARG1), which has potential for treating genetic diseases. Researchers found that using certain combinations of UTRs increased protein production significantly, with specific UTRs from complement factor 3 (C3) and cytochrome p4502E1 (CYP2E1) showing the best results. These findings are crucial because they can lead to more effective mRNA treatments by ensuring more protein is made from the introduced mRNA, ultimately helping patients with genetic disorders.
Who this helps: Patients with genetic diseases who may benefit from improved mRNA therapies.
Enzymatic excision of uracil residues in nucleosomes depends on the local DNA structure and dynamics.
2012
Biochemistry
Ye Y, Stahley MR, Xu J, Friedman JI, Sun Y +4 more
Plain English This study explores how an enzyme called uracil DNA glycosylase (UNG) removes uracil bases from DNA that is tightly packed in nucleosomes, which are structures made of DNA and proteins. The researchers found that while most uracil bases in nucleosomes were less reactive than those in free DNA, some had even higher reactivity, which is affected by the local structure of the DNA around them. This matters because understanding how UNG interacts with DNA in nucleosomes can provide insights into how cells fix DNA damage, which is important for maintaining genetic stability.
Who this helps: This helps researchers studying DNA repair and potentially patients with genetic disorders related to DNA repair mechanisms.
Feng Y, Xie N, Jin M, Stahley MR, Stivers JT +1 more
Plain English This study looked at how a specific enzyme, PRMT1, changes proteins through a process called arginine methylation, which can influence various biological functions. The researchers found that the process happens rapidly, meaning that PRMT1 quickly attaches and removes the methyl group from a protein called histone H4, which is crucial for gene regulation. Understanding this mechanism is important because it can help in designing better drugs to inhibit PRMT1, which could be beneficial in treating diseases where this process goes awry.
Who this helps: This helps patients and doctors looking for new treatments for conditions related to abnormal protein modifications.
Mechanism and specificity of DNA strand exchange catalyzed by vaccinia DNA topoisomerase type I.
2010
Biochemistry
Stahley MR, Stivers JT
Plain English This study focused on a virus enzyme called vaccinia DNA topoisomerase type I, which interacts with DNA strands in a specific way. Researchers found that this enzyme speeds up the process by which DNA strands stick together by 2 times, but it doesn’t affect how quickly they come apart. The enzyme also strongly prevents the joining of mismatched DNA strands, especially when the mismatches are close to its working site. Understanding these details is important because they reveal how the enzyme helps maintain the stability and integrity of DNA, which is crucial for preventing genetic errors.
Who this helps: This benefits researchers studying DNA repair and viral behaviors, as well as patients needing therapies targeting viral DNA processes.
Conformational consequences of ionization of Lys, Asp, and Glu buried at position 66 in staphylococcal nuclease.
2010
Biochemistry
Karp DA, Stahley MR, García-Moreno B
Plain English This study looked at how certain amino acids (Lysine, Aspartate, and Glutamate) in a stable protein called staphylococcal nuclease change when they gain or lose protons (become ionized). They found that these amino acids' pK(a) values, which help determine how likely they are to ionize, changed significantly—by up to 5 units—compared to what is expected in water. This is important because it shows that the stability of the protein affects these values and suggests a new way to study how proteins fold and remain stable.
Who this helps: This research benefits scientists studying protein stability and design, which can aid in drug development and disease treatment.
High apparent dielectric constant inside a protein reflects structural reorganization coupled to the ionization of an internal Asp.
2007
Biophysical journal
Karp DA, Gittis AG, Stahley MR, Fitch CA, Stites WE +1 more
Plain English This study examined how changes in pH affect a specific protein (the V66D variant of staphylococcal nuclease) and found that when a key part of the protein ionizes, it causes structural changes, specifically the loss of 1.5 turns of a helical structure. The researchers discovered that the effective dielectric constant, which helps describe the protein's environment, appears to be much higher (around 10 or more) than what is seen in dry proteins (about 2-4). This is important because it helps us better understand protein behavior, which can improve calculations for determining certain properties of proteins.
Who this helps: This research benefits scientists studying protein behavior and developing drugs targeting specific proteins.
Structural metals in the group I intron: a ribozyme with a multiple metal ion core.
2007
Journal of molecular biology
Stahley MR, Adams PL, Wang J, Strobel SA
Plain English This study examined a specific type of RNA called group I introns, which are found in bacteria. Researchers created a detailed 3D picture of this RNA structure and found that it contains 18 metal ions that are essential for its shape and functionality. These metals help the RNA to fold properly and carry out its biological roles, which is important for understanding how these molecules work in living organisms.
Who this helps: This research is beneficial for scientists studying RNA and could lead to advances in understanding genetic processes and developing new treatments.
RNA splicing: group I intron crystal structures reveal the basis of splice site selection and metal ion catalysis.
2006
Current opinion in structural biology
Stahley MR, Strobel SA
Plain English This study looked at the structures of a type of RNA called group I introns to understand how they splice, or cut and bind RNA segments together. Researchers found that specific arrangements of RNA bases help the introns identify where to splice, and they discovered that two metal ions play a key role in this process. These findings contribute to our knowledge of RNA behavior, which is important for understanding how genes are expressed and regulated.
Who this helps: This helps researchers studying genetic diseases and RNA biology.
Structural evidence for a two-metal-ion mechanism of group I intron splicing.
2005
Science (New York, N.Y.)
Stahley MR, Strobel SA
Plain English This study looked at the structure of a specific RNA segment, known as a group I intron, to understand how it cuts itself to join two parts of a gene together. Researchers discovered that this RNA uses two metal ions, magnesium (Mg2+), positioned very close together (3.9 angstroms apart), to help make this cut effectively. This finding matters because it shows that both RNA and proteins can use similar methods to perform complex chemical tasks, which could enhance our understanding of cellular processes.
Who this helps: This helps researchers and scientists studying RNA functions and genetics.
Crystal structure of a self-splicing group I intron with both exons.
2004
Nature
Adams PL, Stahley MR, Kosek AB, Wang J, Strobel SA
Plain English This study focused on the structure of a specific type of RNA called a group I intron, which can cut and splice itself without the help of proteins. Researchers captured a detailed image of this RNA at a resolution that shows how it interacts with two segments of RNA called exons. They found that the structure is complex, featuring new arrangements that help the intron correctly identify and cut the exons for splicing. This matters because understanding how these processes work could lead to new insights in genetics and molecular biology.
Who this helps: This helps researchers studying RNA processing and gene therapy.
Plain English This study looked at a specific type of RNA structure called a K-turn, which usually bends in a predictable way. Researchers discovered that some K-turns can actually bend in the opposite direction, depending on their surrounding environment or nearby proteins. This finding is important because it shows there are different ways that RNA structures can form, which could impact how RNA functions in the body.
Who this helps: This benefits researchers studying RNA and its role in diseases.
Crystal structure of a group I intron splicing intermediate.
2004
RNA (New York, N.Y.)
Adams PL, Stahley MR, Gill ML, Kosek AB, Wang J +1 more
Plain English This study examined the detailed structure of a specific RNA molecule involved in the splicing process, which is crucial for creating functional proteins. Researchers found a unique arrangement in the RNA that includes key features like a pseudoknot and multiple helical regions, which are important for the splicing mechanism. Understanding this structure helps clarify how the splicing process works at a molecular level, which is important for advancements in genetics and molecular biology.
Who this helps: This benefits researchers and scientists studying RNA processes and genetic engineering.