FACULTY & RESEARCH

Dr. Alper's laboratory is focused on understanding the regulation of the innate immune response, particularly as it relates to the basis for inflammatory disease.

We investigate the genetic, molecular and cellular basis of brain development and myelination using zebrafish as a model system.

Despite including many different proteins, macromolecular complexes often display minimal enzymatic activity. This suggests that conformational changes and interactions are fundamental to their molecular mechanism. My group uses cryo-electron microscopy to characterize the structure, conformational states and interactions of macromolecular complexes involved in essential cellular processes. We correlate that structural information with biochemical and functional data to establish the mechanism of these remarkable cellular machines.

The Barton lab studies RNA viruses - viral RNA replication - and host-pathogen interactions involving viral RNA and endoribonucleases.

Our research asks how the RNA polymerase II transcriptional machinery and RNA processing factors work together to achieve coordinated synthesis and maturation of messenger RNA (mRNA).

My lab studies how cells use epigenetics to control gene amplifications. We have identified epigenetic pathways that cells use to create transient increases in gene copy number. These copy number changes play roles in tumor development, progression and drug resistance. By understanding the fundamental mechanisms that govern copy number control we hope to allow better cancer therapies.

The Breuss laboratory is interested in genomic (and cellular) mosaicism. We assess its impact on human disease and utilize it as a tool to unravel mechanisms of development and cellular homeostasis. While we are broadly interested in these questions, two of our favorite systems to study are human germ cells and the brain.

Research in our laboratory leverages our expertise in immunology, molecular biology and model systems of liver disease to explore the early and late events that influence the progression of chronic liver disease.

Our group aims to understand how mitochondria reprogramming in tumors impact cellular behaviors that drive progressive and lethal cancer. We use a broad repertoire of biochemistry, cell biology, live cell imaging and animal models to study the impact of mitochondria shape, number and subcellular distribution in metastatic dissemination.

Deciphering the mechanisms underlying increased risk of brain metastases in young women with triple negative breast cancer. These include ovarian estrogen effects on reactive astrocytes that results in paracrine activation of EGFR and TRKB signaling in brain metastatic cells.

The Colgan Lab studies mucosal inflammation with focus on intestinal inflammation in the context of inflammatory bowel disease and other GI diseases. Studies are aimed at understanding how epithelial and endothelial cells coordinate barrier function and inflammatory responses at mucosal surfaces. Our lab takes a multifaceted approach by investigating the relationships between gut microbiota, host immune system, genetic background, and environmental influences as it pertains to mucosal health and disease, with research emphasis on energy metabolism, host-microbe interactions, hypoxia-inducible factor, and innate immunity.

While chromosome linearity is so universal among eukaryotes that we assume it to be evolutionarily advantageous, formidable challenges are presented by linear chromosome ends, as they resemble damage-induced DNA breaks, which are vulnerable to degradation and end-joining pathways that provoke genome instability. Telomeres protect chromosome ends from these hazards, and compromised telomere maintenance is a confirmed driver of both tumorigenesis and degenerative diseases. Our group has uncovered key principles underlying these ‘classical’ protective telomere functions. Moreover, we are discovering that the special properties of telomeres provide cells not only with ‘protective caps’ for chromosomes, but also with remarkable regulatory opportunities. For instance, meiotic telomeres control the assembly/disassembly and functions of two additional key structures, centromeres and the nuclear envelope. These discoveries provide novel rationales for the evolutionary dominance and persistence of chromosome linearity.

Exploring the conditions that foster somatic evolution and discovering cancer vulnerabilities.

Research in the Dunn Lab explores: 1) how eosinophils specialize in different environments, 2) how specialized eosinophils interact with other cells in the environment, and 3) how pro-inflammatory eosinophils may be re-specialized to assist in tissue repair. To address our core questions, we use murine models of allergic disease as well as human organoid tissue cultures to understand how eosinophils respond to environmental signals and how they, in turn, impact their surrounding tissues.

Our group focuses on epigenetic mechanisms regulating normal hematopoiesis and leukemia focusing on MLL-family histone methyltransferases.

Our laboratory is focused on investigating the mechanism and function of signaling through a particular family of receptor tyrosine kinases, the platelet-derived growth factor (PDGF) receptor family, in development of the mammalian neural crest-derived craniofacial skeleton.

Our laboratory focuses on a specific family of homeoproteins, the Six family, and their transcriptional cofactors, Eya and Dach. The Six1 homeobox gene is overexpressed in 50% of primary breast cancers and 90% of metastatic lesions, and its overexpression.

Our lab seeks to define how epitranscriptomic changes impact specificity in protein synthesis across an array of contexts including pediatric bone marrow failure and oncogenesis predisposition

The cerebral cortex is the control center of most of our higher-level brain functions, including thought, language, memory and emotion. During cortical development, billions of neurons and glia must be precisely specified and assembled into the intricate circuits that underlie these complex tasks. Disruption of these processes is associated with many devastating human neurological disorders, including epilepsy, schizophrenia, autism and intellectual disability. Our lab studies several processes involved in the formation and function of neural circuits in the cerebral cortex.

Our lab is interested in understanding the complexities of humoral immunity against rapidly evolving viruses, particularly influenza viruses. Our lab has three major interests: (1) Design vaccines to induce broadly protective antibody responses against influenza viruses, (2) investigate how humoral immunity develops at distinct anatomical locations and impacts immunity against future influenza virus exposures, and (3) define how humoral immunity drives viral evolution.

How does the structure of a genome evolve over time? Our research investigates the molecular causes and phenotypic consequences of the broadly defined family of genomic features known as structural variations (SVs). SVs like aneuploidy, loss-of-heterozygosity, and copy number alteration are pervasive, yet poorly understood genomic elements which contribute significantly to the genotypic and phenotypic diversity of eukaryotic populations. Our current work is addressing many fascinating and important biological questions focused on understanding how SVs arise in the genome, and how these variations contribute to genome stability and evolution, phenotypic diversity, and cellular and organismal fitness.

We are a research laboratory of RNA biologists, technology developers, and data analysts focused on discovering and translating fundamental principles of RNA regulation. A major effort in the lab is to understand how RNA damage and repair are integrated with stress responses by combining method development, bioinformatics, genetics, biochemistry, and cell biology.

The long-term goals of our work are to understand how neuron-glial interactions modulate brain function and contribute to pathology in neurodegenerative disease. Towards this goal, we study the interactions of oligodendrocyte lineage cells with neurons in the adult cerebral cortex.

Our lab studies how cells detect and degrade aberrant RNAs, and how dysregulation of this surveillance process contributes to human muscle development and disease.

Our work focuses on the formation and regulation of chromatin domains and their ultimate roles in epigenetic genome regulation. We are particularly interested in the mechanisms of heterochromatin establishment and function.

Dr. Jordan serves as the Chief of the Hematology Division and directs a research program focused on the development of novel therapies for the treatment of leukemia.

The long-term goal of the lab is to understand the cellular and molecular mechanisms governing the interactions between neurons and glia to build a properly functioning nervous system.

Investigating the mechanisms leading to cellular reprogramming and aging, as well as induced Pluripotent Stem Cell (iPSC)-associated cellular rejuvenation.

The effects of advanced age and alcohol misuse on inflammatory responses after burn trauma or infection.

My laboratory investigates molecular mechanisms of epigenetic regulation and the role of chromatin modifications in human diseases. We use high field NMR spectroscopy and X-ray crystallography to obtain atomic-resolution structures of chromatin-binding proteins and complexes involved in transcription and DNA damage repair.

Cell cycle regulation of DNA replication

Our team studies perinatal determinants of female fertility with a special focus on the relationship between establishment of architecture and functional differentiation of the mammalian ovary.

Our research focuses on identifying molecular mechanisms underlying the assembly of macromolecular complexes, with a focus on multisubunit complexes formed by septin proteins. All cellular processes require the function of multisubunit complexes, and while much attention has been given to solving the final structures of such assemblies, comparatively little is known about how individual subunits adopt oligomerization-competent conformations and find their partner subunits in the crowded, dynamic cellular milieu.

Molecular regulation of the microtubule network in cell division and disease.

The aim of our lab's research is to understand how cells acquire their fates during development and how these processes go wrong in congenital disease. As principal model, we use the zebrafish (Danio rerio) to investigate the earliest development of the cardiovascular system using lineage tracing, genome editing, live imaging, and more.

Systems Biology of Human RNA Regulatory Networks.

Our research program addresses how chromatin regulatory proteins associate with histones in response to chromatin signaling events. We are specifically interested in how histone reader domains associate with modified histones in the chromatin relevant context of the nucleosome. We are using NMR spectroscopy along with other biophysical and structural techniques to build models of these complexes and understand how they are regulated. ​Results of these studies will provide insight into fundamental processes of genome regulation, the etiology of human disease, and lay the groundwork for the development of targeted therapeutics.

The Nelson Lab is focused on how sensory thresholds are established during development and how sensory processing deficits lead to human neurological disease. We use the larval zebrafish and a set of mutants identified through genetic screens aimed at identifying molecular and cellular mechanisms of sensory threshold establishment during development and sensory threshold plasticity through habituation. To better understand these mechanisms, we use a variety of techniques including behavior recording and analysis, whole brain activity mapping, and pharmacology.

We are interested in the mechanisms that keep development on track, even when cells are faced with deleterious changes like genetic mutations.

Centrosome and cilia biology in cell division, motility, and disease.

Interplay between inflammation and metabolism as a driver of leukemia development; targeting of pre-malignant and malignant blood-forming stem cells.

Dr. Potter and other University of Colorado Alzheimer’s and Cognition researchers are developing novel diagnostics and treatments for neurodegenerative diseases including Alzheimer’s disease (AD) and Down syndrome (DS), which invariably leads to AD brain pathology by age 30-40. Research spans multiple approaches from biochemistry, cell and chromosome biology, exosomes, cerebral organoids, drug repurposing, and animal models, and then translating the discoveries into diagnostic and intervention trials in humans. One recombinant protein drug discovered by this process has benefited AD patients in its first clinical trial and is being further tested in AD and DS. Several other molecules show great promise.

Regulation of cell division, cell polarity and cell migration.

We are interested in understanding how our genome packaging changes dynamically as cells change their identities and when cells respond to different stimuli. We also exploit our knowledge of how different cell types package their genome to identify disease states using protected cell free DNA fragments in our bloodstreams.

Our lab is working on three main projects: (1) Identify pathways within the fat body that control organismal fat; (2) Determine the role in body fat regulation of a putative nutrient-responsive modifier of physical activity; and (3) Develop a functional map of neuronal control of body fat.

The focus of my research is on the role of sex steroid receptors in breast and gynecological cancers, mechanisms of resistance to hormone therapy, and the differences between hormone dependent and independent breast cancers.

Our goal is to understand how translation impacts mRNA stability, and to place gene regulation in the contexts of broader biological processes.

The Russo lab is interested in understanding how bacterial pathogens interact with their hosts. As a model, we investigate the pathogenesis of Shigella flexneri, which infects cells of the colon and causes diarrhea in humans.

Our lab uses zebrafish to study transcriptional and epigenetic control of key transitions during embryogenesis. We are particularly interested in understanding the onset of zygotic transcription at the maternal-to-zygotic transition, ​and in unraveling the transcription orogram driving neural cell fates beginning during gastrulation.

We are interested in how life experience guides the development and adaptation of the mammalian nervous system. We recently discovered that, in mice, olfactory experience regulates the relative birthrates of the > 1000 distinct olfactory sensory neuron subtypes in an odor-specific manner. These findings have led us to hypothesize that life-long olfactory sensory neurogenesis performs an unknown adaptive role, in addition to the known reparative one. We are currently investigating the mechanism and function of this phenomenon. These studies are anticipated to elucidate fundamental aspects about how the olfactory system develops, adapts, and frequently loses function with age and disease.

The Sartorius laboratory studies the role of sex steroid hormones and their cognate receptors (i.e. estrogen receptor (ER) and progesterone receptor (PR)) in breast cancer.

The overall goal of the Sikora Laboratory is to understand mechanisms of response and resistance to steroid hormones and anti-estrogen therapies in breast cancer, with a special emphasis on invasive lobular carcinoma of the breast.

We are interested in the molecular mechanisms regulating pancreatic islet function in normal and disease conditions. In particular, we study the transcriptional programs, long non-coding RNAs, and RNA processing events that regulate pancreatic identity and function and how disruption of these programs leads to islet dysfunction and diabetes.

We study how the expression of genetic information is spatially regulated within a cell.

The Tamburini lab focuses on understanding how dendritic cells interact and traffic through the lymphatic vasculature to facilitate an appropriate immune response. Specifically, we are interested in mechanisms of antigen archiving, PD-L1 reverse signaling, and tissue specific responses in the liver. As a mentor I strive to be open-minded, learn from my mentees and accept differing opinions. In the last 5 years I have taken NIH and University offered mentorship, bias and equity trainings to improve my mentorship and promote an inclusive and diverse laboratory environment.

Research in the Tucker Lab focuses on developing new tools to sense and manipulate the intracellular environment, and using these tools to understand dynamic cellular processes. A major focus is in developing ways that we can inducibly regulate and control fundamental molecular events such as protein trafficking, proteolysis, gene expression, and intracellular signaling using inducers such as light (optogenetic tools) or chemicals.

The van Dyk lab studies the interactions between virus and host in health and disease. Specifically, our work focuses on gammaherpesviruses.

The research in the Vázquez-Torres lab uses state-of-the-art biochemical, genetic and molecular biology approaches to understand the molecular mechanisms by which reactive species mediate resistance of macrophages against intracellular bacteria, as well as the adaptive strategies that boost antioxidant and antinitrosative defenses of pathogenic bacteria.

We use mice and primary mouse and human cell culture to study how multiciliated cells adopt their cell fate, build cilia and orient the cilia for directional clearance. We investigate the pathways that drive these processes during normal development and regeneration and study how they are misregulated in human disease. Our research has the potential to develop novel biomarkers and therapeutics for individuals suffering from chronic airway diseases.

We develop NMR methods and apply them together with other biophysical methods to study biologically relevant systems at atomic resolution: Diverse dynein motor adaptors and their cargos, allostery in key cell regulator Pin1, Olduvai domains involved in brain function and disease, and various RNA and DNA segments.

The Watt lab is interested in understanding how pathogenic variants in subunits of RNA Polymerases I and III give rise to craniofacial differences and investigating the molecular and cellular basis of genetic disorders affecting craniofacial development. 

Transcriptional regulation of mouse embryonic development.

My lab focuses on developing technologies that enable tracking the full life cycle of proteins in real time with high spatiotemporal resolution in their native intracellular environments. This will help us understand when, where, and how proteins are synthesized, folded, modified, and degraded in both healthy and diseased cells.

My lab studies the mechanism of pre-mRNA splicing and the role of the Six1/Eya transcriptional complex in cancer. We are also developing small molecule or RNA-based approaches to target splicing or the Six1/Eya complex as potential cancer therapeutics

Our major focus over the last five years has been to understand the role of the hexose transporter Glut1 in mammary tumorigenesis.

We study how ion channel activity (bioelectricity) contributes to morphological development in multiple tissues (craniofacial structures, fly wings, brain, pancreas, and bone).

My research interests focus on hormone/growth factor signaling and cancer. Specifically, our laboratory is studying the role of selective protein kinase C (PKC) isoforms in the modulation of cell growth and death in endometrial cancer.

My lab is interested in understanding the molecular basis of essential processes that regulate gene expression. We use biophysical, biochemical methods, and structural methods, including X-ray crystallography. Our insights into these fundamental mechanisms will contribute to a better understanding and ability to regulate gene expression processes involved in human diseases and will assist in drug development efforts. Our studies focus on the following questions: (1) How is chromatin structure modulated for DNA-dependent processes? and (2) How do transcription factors and pioneering factors activate gene expression?

Research interests include: (1) CAR T and engineered T cell therapies of autoimmune diseases; (2) Mechanisms of T cell mediated metal hypersensitivities; (3) Mechanisms of T cell recognition of autoantigens in Type 1 diabetes and RA; and (4) Redox signaling and drug design in the immune diseases and infectious diseases.

Cytoplasmic mRNA regulation is very important during oogenesis, early embryogenesis, and during stem cell divisions that occur throughout development. The mechanisms that regulate cytoplasmic mRNAs and that tie this control to the development of living cells are poorly understood. Recent studies hint that the mechanisms are similar in many animals and that they are important for various human diseases. We are exploring this problem in the small nematode worm, Caenorhabditis elegans.

My laboratory’s goals include understanding how the nuclear proteins Early B cell Factor (EBF) and Pax5 (B cell-specific activator protein) regulate B lineage specification, commitment and the immune response to antigens.

Dr. Holers research group performs both basic and translational research. A longstanding interest has been to decipher the roles of complement receptors and membrane regulatory proteins in the immune response, with a special emphasis on autoimmune diseases.

To distinguish the role of HIF-1a and HIF-2a in cancer progression, Molecular Mechanisms of Hypoxic Transcriptional Response.

(1) Mechanistic understanding of TBI-caused neuroinflammation and neurological deficits; (2) Characterization of trisomy 21-related neurovascular dysfunction by using TBI as a sensitizing probe; (3) Development of mechanism-based immunomodulatory biologics that target the excessive inflammation underlying many disease conditions including TBI-caused vision loss and inflammatory skin disorders.

Regulation of Cell Death by the Protein Kinase C Family: Implications for Tissue Damage and Tumorigenesis.

Mycobacterium tuberculosis survival during latent disease.