In the Glass Lab, we are interested in understanding how epigenetic signaling regulates gene expression, and how alterations in these pathways are involved in disease development, particularly cancer, heart, and infectious disease. We are investigating the molecular mechanisms driving the recognition of histone post-translational modifications in order to identify new therapeutic strategies.

The combinations of marks that make up the histone code have been difficult to decipher, and how multiple modifications modulate protein recognition is not well understood. We aim to determine how physiologically abundant combinations of histone modifications regulate chromatin reader activity to influence disease progression. To address our research questions, we use a diversity of approaches in molecular biology, genomics, biochemistry, biophysics, and proteomics.

The Glass lab is located in the Firestone Medical Research Building in the Larner College of Medicine at the University of Vermont. Dr. Glass is a faculty member in the Departments of Biochemistry and Pharmacology. Dr. Glass is also a member of the UVM Cancer Center, the Cardiovascular Research Institute, and the Vermont Center for Immunobiology and Infectious Disease.  Follow the Glass lab on Twitter and Facebook!

For those interested in joining our lab, please note that scholarships are available for Ph.D. students.

Glass Lab current members:

Karen C. Glass, Associate Professor

Karen Glass

James Lignos, Ph.D. Student

James Lignos

Bohan Liang, M.S. in Pharmacology student

Bohan Liang headshot

Annika Lothrop, Biochemistry student

Annika Lathrop headshot

Ajit Singh, Postdoctoral Fellow

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Kiera Malone, Ph.D. Student

Elizabeth Cook

Elizabeth Cook, M.S. in Biochemistry student

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UVM cancer center logo REDUCEDGlass Lab Research


Even though the DNA in all of our cells is nearly the same, it is epigenetic factors, including modifications to DNA, RNA, and chromatin, that control the gene expression patterns in different cells, under various environmental conditions, and at specific times1. Post-translational modifications on histone tails function as a very complex code for controlling gene expression. Deciphering this code is at least as important as the genetic code for understanding its role in stem cell programming, maternal effects during fetal development, and potential reversibility in cancer therapies. However, it is also orders of magnitude more complex2. We study the molecular mechanisms driving the recognition of histone modifications, and how combinations of these chemical signals regulate protein interactions on the nucleus in both normal and disease states.

Major research efforts in the lab include:

·         To uncover how multiple chromatin reader domains cooperatively regulate the activity of epigenetic regulatory complexes.

·         To reveal how cross-talk between epigenetic marks modulates the function of histone binding proteins and chromatin remodeling enzymes.

·         To identify and functionally characterize how acetyllysine signaling and recognition contributes to the pathogenesis of parasitic infections.

·         To correlate how altered epigenetic modifications influence the progression of cancer, heart, and infectious disease.


The human genome is compacted into chromatin, allowing nearly three meters of DNA to fit into the small volume of the nucleus. Chromatin is composed of DNA and proteins, and this DNA-protein complex is the template for a number of essential cell processes including transcription and replication. Understanding the role of chromatin’s higher order structure in transcriptional control is important as loss of this regulation underlies many disease processes.

The basic structural unit of chromatin is the nucleosome. Nucleosomes are comprised of 147 base pairs of DNA wrapped around a core histone octamer. The histone octamer contains two molecules of each histone H2A, H2B, H3 and H4. Each of these core histones contains two separate functional domains; a globular domain, which interacts with the DNA and other histones, and a flexible tail domain that protrudes from the nucleosome. The tail domains can be modified by the reversible addition of chemical groups such as acetyl-, methyl- and phospho- groups.

Modifications on the histone tail have been shown to be important in altering chromatin structure, facilitating access for DNA-binding transcription factors, but they also act as markers, allowing non-histone proteins to interact with the chromatin. The “Histone Code Hypothesis” suggests that histone tail modifications constitute an epigenetic (beyond genes) code, which is read by other proteins. It postulates that these proteins, and protein complexes are able to recognize/read distinct tail modifications, just like a language or code. This consequently triggers downstream events resulting in unique and specific biological outcomes such as: cell death, cell cycle regulation, and the transcription, repair, or replication of DNA.  

Recent Work

Epigenetic signaling by histone post-translational modifications

We are investigating the structure and function of chromatin binding domains, including the bromodomain, which interact specifically with acetylated histones. There are about 60 human bromodomain-containing proteins, and these nuclear proteins have a wide variety of biological activities3. Bromodomains bind to specific acetylation marks on the histone tail, and tether associated proteins and enzymatic complexes to histones to regulate chromatin structure and gene expression4. However, how these protein modules differentiate between multiple acetylated lysine residues, that are often found alongside other post-translational modifications, to read the histone code is unknown. We recently established the molecular basis of histone acetyllysine recognition by the ATAD2 and ATAD2B bromodomains and discovered that theses bromodomains prefer to interact with histones H4, H2A, and the H2A.X histone variant when they contain multiple acetylated lysine residues. The structural and mechanistic details of histone recognition by bromodomains is crucial for the development of new therapeutic interventions and molecular tools to study a variety of diseases. Our research has fundamentally advanced our understanding of how bromodomains recognize and select for acetyllysine marks.

Insert: Figure 1


Figure 1: Multiple modifications on individual histone tails of the nucleosome modulate the ATAD2/B bromodomain activity. In the cell, ATAD2/B is localized at the chromatin, which is enriched with histone PTMs. These modifications influence the ATAD2/B bromodomain activity. Adjacent methyl groups negatively regulate the ATAD2 bromodomain's ability to recognize the ‘Kac’ mark but do not significantly affect recognition of acetylated histones by the ATAD2B bromodomain.

Bromodomain-containing proteins in cardiovascular and infectious diseases

Plasmodium falciparum is a unicellular protozoan parasite that causes malaria infections in humans. Malaria is a significant global health problem that affected 247 million people in 2021, resulting in approximately 619,000 deaths5. Unfortunately, this disease disproportionally affects infants and children, and the cases have been expanding since 2016 due to climate changes and drug resistance5. In humans, P. falciparum first replicates in the liver cells, and as the disease progresses, it moves into the red blood cells (RBCs)6. The symptoms of malaria are associated with repeated rounds of parasite replication, egress, and invasion into the red blood cells7. At the red blood cell stage of infection, P. falciparum consumes the RBCs hemoglobin, preventing it from carrying oxygen to the heart, which results in anemic heart failure8. In addition, parasitized RBCs stick to the wall of blood vessels in the heart and brain to evade the immune system, which often leads to inflammation and causes blood vessel blockage in these vital organs. These infection-related complications are directly associated with the invasion of RBCs by the parasite. The P. falciparum Bromodomain Protein 1 (PfBDP1) is a multi-domain nuclear protein that contains a unique combination of ankyrin repeats (ANK) followed by a bromodomain (BRD) (Fig. 2A). In-vivo studies have demonstrated that association of PfBDP1 with acetylated chromatin at the promoters of invasion genes promotes their expression, and knockdown of PfBPD1 strongly reduces expression, and blocks the invasion of RBCs (Fig. 2B)9,10. The chromatin binding activity of PfBDP1 is thought to play an essential role in the red blood cell invasion process by controlling the expression of genes that are required for cell entry. Thus, it is imperative to understand the essential factors involved in the P. falciparum RBC invasion process to develop therapeutic interventions.

Insert: Figure 2

Figure 2. Role of PfBDP1 in regulating the expression of invasion related genes. (A) Domain organization of PfBDP1. (B) (top) Recognition of acetylated lysine by PfBDP1 bridges it to chromatin where it activates the transcription of invasion related genes. (bottom) Knock-down of PfBDP1 prohibits this interaction, preventing parasite invasion.

The focus of my research is aimed at determining the structures of chromatin binding domains, including the bromodomain and PHD finger, in complex with the histone tail to elucidate how histone tail modifications are recognized. This research will aid in a deeper understanding of how chromatin remodeling complexes are targeted to the chromatin and regulate gene expression.  A greater understanding of how these molecular signaling pathways function and are regulated will provide insights into how they can be therapeutically manipulated, and may help to identify new diagnostic markers and targets to prevent and treat disease.


  1. Time Magazine 172(2010).
  2. Nat Chem Biol 14, 206-214 (2018).
  3. Cell 149, 214-31 (2012).
  4. FEBS Lett (2014).
  5. https://www.who.int/publications/i/item/9789240064898, 2022).
  6. Cold Spring Harb Perspect Med 7(2017).
  7. Med Microbiol Immunol 201, 593-8 (2012).
  8. Hematology Am Soc Hematol Educ Program, 35-57 (2002).
  9. Cell Host Microbe 17, 741-51 (2015).
  10. Front Cell Dev Biol 10, 816558 (2022).