Cellular & Molecular Medicine

Shanna Hamilton

Assistant Professor, Cellular and Molecular Medicine
Member of the Graduate Faculty
Primary Department
Department Affiliations

Work Summary

Abnormal intracellular calcium handling is implicated in many cardiovascular diseases and can lead to arrhythmias and sudden cardiac death. The overarching goal of the Hamilton laboratory is to decipher molecular mechanisms of calcium regulation in the healthy and diseased heart, with the end goal of uncovering novel therapeutic strategies to treat arrhythmias and heart disease.

Research Interest

Dr. Hamilton is an Assistant Professor and Principal Investigator in the Department of Cellular and Molecular Medicine (CMM), University of Arizona College of Medicine Tucson. Dr. Hamilton received her Ph.D. in Biophysics at Cardiff University and completed her postdoctoral training in Cardiovascular Physiology at Brown University, as well as The Ohio State University. In her laboratory, Dr. Hamilton's research focuses on calcium signaling in the heart, and how irregularities in calcium signaling contribute to both inherited and acquired cardiovascular diseases. By using a multi-level approach, from molecule-cell-organ-organism, Dr. Hamilton is uncovering new molecular mechanisms of calcium regulation and finding new therapeutic strategies to treat these diseases.

Ghassan Mouneimne

Assistant Professor, Cancer Biology - GIDP
Associate Professor, Cellular and Molecular Medicine
Member of the Graduate Faculty
Primary Department

Work Summary

Research in our laboratory is focused on understanding how aberrant structural organization of the cytoskeleton influences cellular behavior, such as cancer cell invasion and metastasis. The regulation of cellular behavior by structural remodeling of the cytoskeleton exemplifies the paradigm of “structure regulates function” at the cellular level. Our goal is to identify distinct actin cytoskeletal architectures that impact the response of cancer cells to well-known genetic and microenvironmental factors during cancer progression.

Research Interest

Our research program at the Mouneimne Laboratory concentrates on understanding how hormonal regulation of the cytoskeletal architecture in Estrogen Receptor positive (ER+) Breast Cancer (BC) cells impact their response to the biophysical tumor microenvironment (TME), particularly matrix rigidity. We have established that, through remodeling of the cytoskeleton, ER has dichotomous roles in promoting and suppressing ER+ BC invasion in stiff and soft TMEs, respectively. This differential responsiveness to the biophysical TME, we find, is unique to ER+ tumors and play a distinct role in promoting their metastatic dissemination, which is one of the major focus areas of our group. Further, we are interested in determining the mechanism by which these metastatic properties are maintained after dissemination to distant sites, such as the bone, where ER+ BC cells could remain dormant for several years before progressing to overt bone metastases. Our goal is to identify unique vulnerabilities in ER+ BC tumors potentially valuable for targeting cancer cells in both the neoadjuvant and adjuvant setting, thus blocking progression of initial and residual disease, respectively. The expertise of my group is in two converging areas of analytical cell biology, exploiting quantitative microscopy, and cancer biology, modeling invasive and metastatic phenotypes of breast cancer both in vitro and in vivo. Further, in collaboration with breast oncologists, pathologists, biophysicists, and biomedical engineers, our team is tackling the problem of ER+ BC metastasis from diverse angles, rationales, and training backgrounds, broadening our approach to include basic, translational, and patient-oriented research strategies.

Darren A Cusanovich

Assistant Professor, Cellular and Molecular Medicine
Assistant Professor, Research Scholar Track
Assistant Research Scientist
Contact
(520) 626-8639

Work Summary

Working at the nexus of functional genomics, computational biology, and cellular biology, our group is both experimental and computational. We develop novel single-cell genomic technologies and apply them to better understand lung development and disease.

Research Interest

Dr. Cusanovich received his B.S. in Music Business from Loyola University New Orleans in 2002. After a brief stint in the music industry in Los Angeles, he realized that his true passion was genomics. So, Dr. Cusanovich spent a few years in Donata Vercelli's Lab here at the University of Arizona - his first exposure to asthma genomics research. Dr. Cusanovich then got his Ph.D. in Human Genetics from The University of Chicago (in Yoav Gilad's lab). While there, Dr. Cusanovich studied how genetic variation in human populations perturbs gene expression and can lead to complex disease susceptibilities. Dr. Cusanovich then did his postdoctoral research in Jay Shendure's lab at the University of Washington. While in Seattle, he developed a novel single-cell chromatin accessibility assay and applied it to several model systems to study the variation in gene regulatory landscapes present in complex tissues. In 2018, Dr. Cusanovich accepted a position here at the UofA in Cellular and Molecular Medicine and the Asthma and Airway Disease Research Center. The Cusanovich Lab is interested in understanding how the human genome regulates itself to bring about all of the cellular diversity present in our bodies. In addition, we are interested in how genetic variation and environmental exposures in human populations impact that regulation and sometimes lead to complex disease. The particular disease model that we focus on is asthma, a complex disease affecting ~10-20% of the population. To study these phenomena, we use single-cell genomics technologies so that we can evaluate the impact of genetic and environmental variability from the perspective of whole tissues rather than having to isolate individual cell types or use simplistic cellular models. Lab website: cusanovichlab.github.io

Jared Churko

Assistant Professor, Cellular and Molecular Medicine
Director, iPS Cell Core
Assistant Professor, Biomedical Engineering
Assistant Professor, Genetics - GIDP
Assistant Professor, Physiological Sciences - GIDP
Member of the Graduate Faculty
Assistant Professor, BIO5 Institute
Primary Department
Contact
(520) 626-2347

Research Interest

The BIO5 is the most influential cross collaborative initiative at the University of Arizona. Being a part of the BIO5 opens opportunities to collaborate within scientific fields outside of my specialty and promotes both academic and industrial partnerships. With my background in single-cell transcriptomics, hiPSC technology and heart disease, I hope to share my knowledge and learn from other BIO5 members. In becoming a member of BIO5, I aspire to enhance my research program an ultimately, make life changing discoveries.

Brett Colson

Assistant Professor, Cellular and Molecular Medicine
Assistant Professor, Physiological Sciences - GIDP
Assistant Professor, Biomedical Engineering
Assistant Professor, Clinical Translational Sciences
Member of the Graduate Faculty
Assistant Professor, BIO5 Institute
Primary Department
Contact
(520) 621-1950

Research Interest

The research goal of my laboratory is to understand the molecular motions and interactions of proteins involved in regulating contractile function of healthy cardiac and skeletal muscle, to determine the culprits of contractile dysfunction and remodeling in muscle disorders and cardiovascular disease, and then apply these insights to design novel therapies. We use biophysical approaches, such as time-resolved spectroscopy with site-directed probes to assess protein structural dynamics and mechanical measurements of isolated muscle fibers to assess contractile force and kinetics, in order to establish structure-function relationships inherent to the molecular, biochemical, and physiological mechanisms.

Jean M Wilson

Professor, Cellular and Molecular Medicine
Director, Willed Body Program
Professor, Cancer Biology - GIDP
Professor, Neuroscience - GIDP
Professor, BIO5 Institute
Member of the General Faculty
Member of the Graduate Faculty
Primary Department
Contact
(520) 626-2557

Research Interest

Jean M. Wilson, Ph.D. is a Professor of Cellular and Molecular Medicine at the University of Arizona and member of the Arizona Cancer Center. Dr. Wilson’s work focuses on the establishment and maintenance of the mucosal barrier of the intestine. The cells of the intestine provide a selective barrier to pathogens and toxins, and loss of this barrier function is fundamental to pathologies such as inflammatory bowel disease and bacterial infection. In addition, loss of cellular interactions important for barrier function may predispose these cells to cancer. Work in Dr. Wilson’s laboratory focuses on a protein that is highly expressed in developing intestine, implying a critical role in the formation of the intestinal epithelium. Disruption of this protein compromises junctional integrity and epithelial polarity. Furthermore, expression of this protein is decreased in a model of neonatal necrotizing enterocolitis, a disease of newborns with high morbidity and mortality. These findings implicate this protein in the maintenance of intestinal barrier function in the neonate. In addition, continued expression in the adult intestine positions it to regulate epithelial permeability and polarity throughout life. Our studies focus on protein partners that interact with this protein with the goal of identifying the molecular machinery that regulates this pathway.

Donata Vercelli

Professor, Cellular and Molecular Medicine
Regents Professor, Cellular and Molecular Medicine
Director, Arizona Center for the Biology of Complex Diseases (ABCD)
Associate Director, Asthma / Airway Disease Research Center
Professor, Genetics - GIDP
Professor, BIO5 Institute
Member of the General Faculty
Member of the Graduate Faculty
Primary Department
Contact
(520) 626-6387

Research Interest

Donata Vercelli, MD, is a Professor of Cellular and Molecular Medicine, the Associate Director of the Arizona Respiratory Center and the Director of the Arizona Center for the Biology of Complex Diseases. Her research work is at the cutting edge of the immunology and genetics of complex lung diseases. Her laboratory spans both human and animal models. After characterizing cellular and molecular events critical for the regulation of human IgE synthesis, she became interested in the mechanisms through which natural genetic variants modify susceptibility to complex diseases, particularly allergy and asthma. To this purpose, she developed innovative, unique mouse models in which distinct human haplotypes of asthma- and allergy-associated genes are carried by BAC transgenic mice and can be directly compared for their regulatory properties in vivo. The unexpected, essential mechanisms underpinning the involvement of Th2 cytokines in allergy and asthma revealed by this mouse model have been fully validated in human populations. Dr. Vercelli's work on the epigenetic regulation of Th2 cytokine expression in human neonatal T cells revealed novel facets of early life regulatory events and her continued interest in epigenetics has led to the first demonstration that neonatal DNA methylation signatures in innate immunoregulatory pathways predict asthma during childhood. Most recently, Dr. Vercelli has devised a highly innovative approach that combines epidemiologic, biochemical and mouse model studies to dissect the mechanisms underlying the asthma-protective and asthma-promoting effects of two distinct US farming environments (Amish and Hutterite). Such studies are likely to critically advance our knowledge about fundamental mechanisms of asthma pathogenesis.

Vercelli Lab Website

Curtis Thorne

Associate Professor, Cellular and Molecular Medicine
Assistant Professor, BIO5 Institute
Member of the General Faculty
Member of the Graduate Faculty
Primary Department
Contact
(520) 626-0395

Work Summary

We combine chemical and computer vision approaches to discover how regenerative tissues process environmental information to promote accurate cell fate decisions and prevent uncontrolled cell growth.

Research Interest

We study control of cell fate and self-organization in intestinal renewal and drug response in cancer. Utilizing the fascinating characteristics of intestinal stem cells combined with chemical biology and computational image analysis approaches, we are addressing fundamental questions of multicellular systems: How do cells identify, measure, and respond to each other and to their environment? What are the signals that control the renewal and regeneration of tissues? How do these signals become defective in colorectal cancer? Our long-term goal is to uncover an underlying circuit theory behind these behaviors – a set of predictive principles that tell us how complex functionality arises from simpler biological components. We have a particular interest in kinase networks that regulate healthy tissue homeostasis and become damaged in cancer. Through our quantitative high-throughput imaging and drug discovery efforts, we are finding new ways to understand and repair these networks. Keywords: Stem cells, Cancer, Regeneration, Drug discovery

Casey E Romanoski

Associate Professor, Cellular and Molecular Medicine
Associate Professor, Clinical Translational Sciences
Associate Professor, Genetics - GIDP
Associate Professor, BIO5 Institute
Primary Department
Department Affiliations
Contact
(520) 626-7244

Work Summary

My laboratory aims to identify the genetic and environmental reasons that certain individuals are predisposed to develop complex diseases like heart disease. We use new technologies, experimental, and computational approaches to identify molecular patterns indicative of disease predisposition.

Research Interest

Our laboratory is both experimental and computational. We use next-generation sequencing technologies to measure genome-wide molecular phenotypes. By leveraging the interconnected relationships between DNA sequence, transcription factor binding, chromatin modification, and gene expression, we study how cells achieve context-appropriate expression patterns and signal responsiveness. Lab Website: www.romanoskilab.com Keywords: Genetics, Genomics, Vascular Biology, Bioinformatics

Gregory C Rogers

Professor, Cellular and Molecular Medicine
Associate Professor, Cellular and Molecular Medicine
Associate Head, Faculty Development
Associate Professor, Cancer Biology - GIDP
Associate Professor, Molecular and Cellular Biology
Associate Professor, Genetics - GIDP
Associate Professor, BIO5 Institute
Primary Department
Contact
(520) 626-3925

Research Interest

Gregory C. Rogers, PhD, is an Assistant Professor at the University of Arizona College of Medicine in the Department of Cellular and Molecular Medicine. His laboratory is located in the University of Arizona Cancer Center.The Rogers laboratory is interested in the molecular mechanisms cells use to maintain stability of their genomes. This is medically relevant because genomic instability can promote tumorigenesis. During mitosis, cells face particular risk, as errors in chromosome segregation can lead to chromosome instability (CIN) which is characterized, in part, by an abnormal chromosome complement (known as aneuploidy). Indeed, aneuploidy promotes malignant transformation and is an underlying cause of birth defects. Mitotic spindles are used to faithfully segregate chromosomes into daughter cells and, for this to occur properly, it is critical that cells assemble spindles with a bipolar fusiform-shape. Cells control spindle shape using centrosomes, tiny organelles that nucleate the microtubule cytoskeleton and organize the two spindle poles. Normally, cells contain a single centrosome which duplicates once per cell cycle, thus ensuring that cells enter mitosis with only two centrosomes to build a bipolar spindle. Cancer cells, however, overduplicate their centrosomes, which leads to multipolar spindle formation and chromosome instability. In fact, most human tumors contain cells with elevated centrosome numbers and aneuploid genomes. Importantly, the fundamental mechanisms that cells use to control their centrosome number are unclear, nor is it understood how this regulation goes awry in cancer. His work centers on characterizing a particular pathway (the Plk4 pathway) to control the biogenesis of centrosomes. This pathway utilizes both phosphorylation and ubiquitin-mediated proteolysis as regulatory mechanisms in a complex signaling pathway to control the biogenesis of centrosomes.