Jamie E Denizio

Department of Biochemistry and Biophysics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.

22 publications 2013 – 2023

What does Jamie E Denizio research?

Jamie E Denizio studies how gene editing technologies, specifically CRISPR, can be applied to manage cholesterol levels in the body. They work on disabling a particular gene called PCSK9, which plays a crucial role in cholesterol production within the liver. Their research aims to provide a long-lasting solution for heart disease patients, moving away from the need for ongoing cholesterol medications. By using CRISPR, they can achieve significant drops in cholesterol levels with just a single treatment, making it a potential game-changer for managing heart health.

Key findings

  • In a study involving monkeys, a single injection of CRISPR technology resulted in a 60% reduction in cholesterol levels that remained low for at least 8 months.
  • The CRISPR-based treatment targets the PCSK9 gene, which is responsible for cholesterol regulation, showing promise for long-term management of cholesterol without daily medication.
  • This research suggests that gene editing could provide a one-time treatment option for patients, significantly altering the approach to preventing heart disease.

Frequently asked questions

Does Dr. Denizio study heart disease?
Yes, Dr. Denizio focuses on heart disease, specifically looking at how gene editing can be used to manage cholesterol levels.
What treatments has Dr. Denizio researched?
Dr. Denizio has researched a revolutionary gene-editing treatment using CRISPR to disable the PCSK9 gene that controls cholesterol production.
Is Dr. Denizio's work relevant to patients with high cholesterol?
Absolutely, their work is highly relevant as it explores a potentially permanent solution for managing high cholesterol without the need for ongoing medication.

Publications in plain English

Direct enzymatic sequencing of 5-methylcytosine at single-base resolution.

2023

Nature chemical biology

Wang T, Fowler JM, Liu L, Loo CE, Luo M +11 more

Plain English
This study focused on a new method called DM-Seq, which can identify a specific DNA modification called 5-methylcytosine (5mC) without damaging the DNA. Researchers found that DM-Seq accurately detects 5mC in very small amounts of DNA and provides more reliable results than traditional methods that can confuse 5mC with similar modifications. This is important because it allows for better understanding of DNA changes in clinical tumor samples, which can be significant for cancer prognosis. Who this helps: This helps doctors and researchers studying cancer and other diseases.

PubMed

Tuning Hsp104 specificity to selectively detoxify α-synuclein.

2023

Molecular cell

Mack KL, Kim H, Barbieri EM, Lin J, Braganza S +10 more

Plain English
This study focused on improving a protein called Hsp104, which helps break down harmful protein clumps linked to diseases like Parkinson's. The researchers created special versions of Hsp104 that target only the specific harmful protein α-synuclein, finding that these versions can reduce toxicity effectively—cutting down nerve cell damage by enhancing how α-synuclein is managed. This matters because it offers a more precise way to tackle neurodegenerative disorders without affecting other important proteins that could cause unwanted side effects. Who this helps: This benefits patients with neurodegenerative diseases, particularly those with Parkinson's, and the doctors treating them.

PubMed

Functionally distinct roles for TET-oxidized 5-methylcytosine bases in somatic reprogramming to pluripotency.

2021

Molecular cell

Caldwell BA, Liu MY, Prasasya RD, Wang T, DeNizio JE +9 more

Plain English
This study looked at how certain enzymes in the body help change regular cells into more versatile stem cells, which can develop into different types of cells. The researchers found that only specific forms of these enzymes, which can convert a chemical change in DNA up to a particular point, were able to restore the ability of certain mouse cells to transform into stem cells. This is important because understanding this process can lead to better methods for making stem cells, which have significant potential for medical treatments. Who this helps: This helps patients needing regenerative therapies and doctors looking for better ways to assist in stem cell research.

PubMed

TET-TDG Active DNA Demethylation at CpG and Non-CpG Sites.

2021

Journal of molecular biology

DeNizio JE, Dow BJ, Serrano JC, Ghanty U, Drohat AC +1 more

Plain English
This study examined how certain enzymes in our cells remove chemical modifications from DNA, specifically looking at two types of DNA sequences (CG and non-CG). The researchers found that while one enzyme (TET2) works better on CG sequences, it can still function on non-CG ones, and another enzyme (TDG) is less affected by the type of sequence when removing modified parts of DNA. Understanding this process is important because it helps us learn how our DNA can be regulated, which has implications for biological functions and diseases. Who this helps: This helps researchers and doctors working on genetic and epigenetic therapies.

PubMed

BET bromodomain protein inhibition reverses chimeric antigen receptor extinction and reinvigorates exhausted T cells in chronic lymphocytic leukemia.

2021

The Journal of clinical investigation

Kong W, Dimitri A, Wang W, Jung IY, Ott CJ +28 more

Plain English
This study looked at why some patients with chronic lymphocytic leukemia (CLL) do not benefit from CAR T cell therapy. Researchers found that blocking certain proteins (called BET proteins) helped restore the functionality of CAR T cells, making them stronger and more effective against the cancer. Specifically, this treatment improved the T cells' ability to grow and fight the disease, suggesting a way to enhance the therapy's success for more patients. Who this helps: This research benefits patients with chronic lymphocytic leukemia who are receiving CAR T cell therapy.

PubMed

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.

PubMed

Selectivity and Promiscuity in TET-Mediated Oxidation of 5-Methylcytosine in DNA and RNA.

2019

Biochemistry

DeNizio JE, Liu MY, Leddin EM, Cisneros GA, Kohli RM

Plain English
This study focused on how TET2, an enzyme, modifies a specific part of DNA and RNA called 5-methylcytosine. Researchers found that TET2 works best on double-stranded DNA, while it struggles to act on double-stranded RNA; in fact, it prefers modified DNA over RNA for its reactions. These findings are important because they help clarify the enzyme's role in gene regulation and could affect how we understand cell functions and diseases related to DNA and RNA modifications. Who this helps: This research benefits scientists and doctors working on genetic diseases and cancer treatments.

PubMed

Infection from Outdoor Sporting Events-More Risk than We Think?

2019

Sports medicine - open

DeNizio JE, Hewitt DA

Plain English
The study examined the infection risks associated with outdoor sporting events, especially those involving contact with mud. It was found that soils and mud at these events can harbor harmful germs, leading to outbreaks of infectious diseases, which is a concern not only for participants but also for people in the surrounding community. To address this issue, the researchers suggest implementing monitoring practices and providing wash stations before and after events to help prevent the spread of infections. Who this helps: This helps athletes, event organizers, and local communities.

PubMed

Harnessing natural DNA modifying activities for editing of the genome and epigenome.

2018

Current opinion in chemical biology

DeNizio JE, Schutsky EK, Berrios KN, Liu MY, Kohli RM

Plain English
This research paper explores how natural enzymes that modify DNA can be used to edit genes more precisely. The authors reviewed different types of these enzymes and explained how understanding their structure and function allows scientists to enhance their abilities to target specific areas of DNA. These advancements are significant because they can improve the accuracy of genetic editing, which has the potential to lead to better treatments for various diseases. Who this helps: This benefits researchers and patients looking for more precise genetic therapies.

PubMed

Disruption of TET2 promotes the therapeutic efficacy of CD19-targeted T cells.

2018

Nature

Fraietta JA, Nobles CL, Sammons MA, Lundh S, Carty SA +33 more

Plain English
This study looked at how a change in a gene called TET2 affected the effectiveness of CAR T cells used to treat a patient with chronic lymphocytic leukemia. The researchers found that 94% of the CAR T cells in the patient came from one cell that had a modified TET2 gene, leading to a complete remission of the leukemia. This matters because it highlights a potential way to make cancer treatments more effective by targeting specific genetic changes in T cells. Who this helps: This helps cancer patients, especially those with B cell malignancies like leukemia.

PubMed

Nondestructive, base-resolution sequencing of 5-hydroxymethylcytosine using a DNA deaminase.

2018

Nature biotechnology

Schutsky EK, DeNizio JE, Hu P, Liu MY, Nabel CS +5 more

Plain English
This study introduced a new method called ACE-seq, which allows researchers to analyze a specific DNA modification (5-hydroxymethylcytosine or 5hmC) using much less DNA—over 1,000 times less than traditional techniques. They applied this method to brain cells and found that 5hmC mainly occurs at specific sites in the DNA, which are important for gene regulation. This research is significant because it enhances our understanding of how DNA modifications work and can help study diseases related to these changes. Who this helps: This helps researchers and doctors studying genetic and neurological conditions.

PubMed

Exploiting Substrate Promiscuity To Develop Activity-Based Probes for Ten-Eleven Translocation Family Enzymes.

2018

Journal of the American Chemical Society

Ghanty U, DeNizio JE, Liu MY, Kohli RM

Plain English
Researchers studied TET enzymes, which play an essential role in modifying DNA. They discovered that these enzymes can interact with modified DNA bases, resulting in detectable changes. Specifically, they found that one modified base, 5-vinylcytosine, leads to a product that helps measure TET activity accurately, allowing for closer tracking of these enzymes in cells. This research is important because it provides new tools to understand how TET enzymes operate, which could have implications for diseases linked to DNA regulation. Who this helps: This benefits researchers and doctors studying genetic diseases and epigenetics.

PubMed

Mutations along a TET2 active site scaffold stall oxidation at 5-hydroxymethylcytosine.

2017

Nature chemical biology

Liu MY, Torabifard H, Crawford DJ, DeNizio JE, Cao XJ +3 more

Plain English
This study looked at how certain changes in a key part of the TET2 enzyme affect its ability to produce specific chemical bases important for gene regulation. Researchers found that by modifying a particular site in the TET2 enzyme, they could create versions that successfully produced one base called 5-hydroxymethylcytosine (hmC) but not the other two bases (5-formylcytosine and 5-carboxylcytosine). This is important because it helps clarify the roles of these chemical bases in gene regulation and could lead to new ways to study their specific functions in the body. Who this helps: This benefits researchers studying gene regulation and diseases related to gene expression.

PubMed

DNA Methyltransferases Demonstrate Reduced Activity against Arabinosylcytosine: Implications for Epigenetic Instability in Acute Myeloid Leukemia.

2017

Biochemistry

Nabel CS, DeNizio JE, Carroll M, Kohli RM

Plain English
This study looked at how a drug called arabinosylcytosine (araC), used to treat acute myeloid leukemia (AML), affects the way DNA is modified in cells. Researchers found that when araC is incorporated into DNA, it is methylated much less effectively than normal DNA, specifically, by more than 200 times less with a key enzyme called DNMT1. This finding is important because it suggests that araC treatment might lead to changes in DNA that could help cancer cells survive and come back after treatment. Who this helps: This benefits patients with acute myeloid leukemia and their doctors by providing insights into treatment challenges and potential relapses.

PubMed

APOBEC3A efficiently deaminates methylated, but not TET-oxidized, cytosine bases in DNA.

2017

Nucleic acids research

Schutsky EK, Nabel CS, Davis AKF, DeNizio JE, Kohli RM

Plain English
This study looked at how a specific enzyme called APOBEC3A (A3A) interacts with different forms of DNA bases, focusing on its ability to change methylated cytosine bases into uracil. The researchers found that A3A effectively modifies methylated cytosine but is highly inefficient at modifying oxidized forms of these bases, being over 3700 times less capable of doing so. Understanding these interactions is important because it sheds light on DNA modification processes, which can influence cancer development and may offer tools for biotechnological applications. Who this helps: Patients with cancer and researchers working on DNA modification therapies.

PubMed

The expanding scope and impact of epigenetic cytosine modifications.

2016

Current opinion in chemical biology

Liu MY, DeNizio JE, Schutsky EK, Kohli RM

Plain English
This study looked at how chemical changes to DNA, especially a process called cytosine methylation, influence how genes behave and help define what kind of cell they are. Researchers discovered new forms of modified cytosine, thanks to a group of enzymes, which could change DNA structures and functions in ways we didn't fully understand before. This is important because it may lead to new insights into how our genes are regulated and how various diseases could be treated. Who this helps: This benefits patients, especially those with genetic disorders or cancers.

PubMed

Quantification of Oxidized 5-Methylcytosine Bases and TET Enzyme Activity.

2016

Methods in enzymology

Liu MY, DeNizio JE, Kohli RM

Plain English
This study focused on understanding the different chemical forms of cytosine in DNA and how TET enzymes modify them. The researchers developed specialized tools to accurately measure five types of cytosine, which include both modified and unmodified versions, to better understand the role of TET enzymes in gene regulation. The methods they created help scientists study how these changes in DNA can impact health and development. Who this helps: This benefits researchers studying gene regulation and potential treatments for diseases influenced by genetic modifications.

PubMed

A peptide from human semenogelin I self-assembles into a pH-responsive hydrogel.

2015

Soft matter

Frohm B, DeNizio JE, Lee DS, Gentile L, Olsson U +3 more

Plain English
This study looked at a peptide from human semen called GSFSIQYTYHV, which can naturally turn into a clear gel when mixed with water at neutral pH. The researchers found that this gel has strong elasticity and forms long, thread-like structures, which suggests it could be used in medical products. This is important because it opens the door for creating new materials that could help deliver drugs or heal wounds with fewer side effects. Who this helps: Patients needing effective drug delivery systems or better wound care solutions.

PubMed

Both tails and the centromere targeting domain of CENP-A are required for centromere establishment.

2015

The Journal of cell biology

Logsdon GA, Barrey EJ, Bassett EA, DeNizio JE, Guo LY +4 more

Plain English
This study looked at how a specific part of the protein CENP-A helps create new centromeres, which are crucial for proper chromosome separation during cell division. Researchers found that two specific areas of CENP-A play important roles in attracting proteins necessary for forming a new centromere; specifically, a small piece of the protein's tail and a region that targets it to the centromere are both essential for this process. Understanding how centromeres are established is important because it helps us grasp how cells divide correctly, which is vital for healthy growth and function. Who this helps: This helps researchers and doctors studying genetic diseases and cancer.

PubMed

PARP-1 Activation Requires Local Unfolding of an Autoinhibitory Domain.

2015

Molecular cell

Dawicki-McKenna JM, Langelier MF, DeNizio JE, Riccio AA, Cao CD +5 more

Plain English
This study examined how the protein PARP-1 activates to help repair DNA when it’s damaged. Researchers discovered that a specific part of PARP-1 unfolds when it interacts with broken DNA, allowing it to function properly. Understanding this mechanism is important because it can lead to better treatments for conditions where PARP-1 is overactive, like certain cancers. Who this helps: Patients with cancer and conditions related to DNA damage.

PubMed

DAXX co-folds with H3.3/H4 using high local stability conferred by the H3.3 variant recognition residues.

2014

Nucleic acids research

DeNizio JE, Elsässer SJ, Black BE

Plain English
This study looked at how a protein called DAXX helps assemble genetic material in cells by working with specific versions of histone proteins, H3.3 and H4. The researchers found that DAXX has a unique way of stabilizing the complex it forms with H3.3 and H4, which makes it very effective at choosing H3.3 over similar proteins, thanks to specific properties at certain recognition sites. Understanding this process is important because it sheds light on how our cells efficiently organize their genetic material, which is crucial for proper cell function. Who this helps: This helps researchers and doctors involved in understanding genetic regulation and potential treatments for diseases related to chromatin mismanagement.

PubMed

Identification and interrogation of combinatorial histone modifications.

2013

Frontiers in genetics

Karch KR, Denizio JE, Black BE, Garcia BA

Plain English
This research focused on how certain chemical changes to histone proteins can influence important cellular functions, like gene activity and cell death. Using advanced mass spectrometry techniques, researchers found ways to identify and measure multiple modifications on histones at the same time. Understanding these modifications is crucial because they play a key role in regulating gene expression and cellular responses, which is important for diseases like cancer. Who this helps: This helps doctors and researchers working on cancer and other diseases related to gene regulation.

PubMed

Publication data sourced from PubMed . Plain-English summaries generated by AI. Not medical advice.