Francois M. Abboud, MD, MACP
- Associate Vice President for Research
- Professor, Department of Internal Medicine – Cardiovascular Medicine
- Professor, Department of Molecular Physiology and Biophysics
- Founding Director, University of Iowa Francois M. Abboud Cardiovascular Research Center
- Edith King Pearson Chair of Cardiovascular Research
- Member, Fraternal Order of Eagles Diabetes Research Center
Publication
“Sympathetic Neural Mechanisms in Obstructive Sleep Apnea.” Journal of Clinical Investigation. 1995 Oct;96(4):1897-904.
Research article summary
Obstructive sleep apnea now afflicts over 30 million adults in the U.S. and is becoming a global epidemic with a risk of sudden death during sleep. This study of obstructive sleep apnea by Dr. Abboud and colleagues was the first to record the heightened sympathetic nerve activity and consequent surges in high blood pressure in otherwise normal patients while they were asleep and stopped breathing repeatedly. The manuscript also reports the benefit of CPAP (continuous positive airway pressure) therapy, the main form of treatment for obstructive sleep apnea today.
Dr. Abboud has held key leadership positions in the Carver College of Medicine— including 26 years as chair and departmental executive officer of the Department of Internal Medicine—while guiding research to advance the understanding and management of cardiovascular disease and stroke. Funded by the National Heart, Lung, and Blood Institute since 1971, his program project grant is the longest continuously funded grant under the same principal investigator.
His numerous honors include the George M. Kober Medal from the Association of American Physicians and memberships in the Institute of Medicine of the National Academy of Sciences and the American Academy of Arts and Sciences.
Michael D. Abràmoff, MD, PhD
- Professor, Department of Ophthalmology and Visual Sciences
- Professor, Department of Electrical and Computer Engineering
- Professor, Department of Biomedical Engineering
- Robert C. Watzke, MD, Professor in Retinal Research
Publication
“Image processing with ImageJ.” Biophotonics International. 2004. Jul;11(7):36-42
Research article summary
Dr. Abràmoff is one of the initial developers of ImageJ, the most widely used open source image analysis program, which is used worldwide for many applications—from skin analysis to neuroscience. This paper describes the creation and design considerations of ImageJ, which is in the public domain and runs on any operating system. The paper covers various topics, including imaging abilities; cross platform use; image formats supported as of June 2004; extensions, including macros and plug-ins; three- and four-dimensional extensions; and imaging libraries. The National Institutes of Health reported millions of downloads of ImageJ, at a rate of about 24,000 per month. A highly knowledgeable community of ImageJ users shares advice on using the program.
Dr. Abràmoff is an internationally renowned physician-scientist and fellowship-trained retina specialist. For the past 20 years, he has studied how autonomous artificial intelligence (AI) can be used to detect disease in medical images. He has authored over 270 peer-reviewed publications, which have been cited over 26,000 times, and he is the primary inventor on 16 issued patents and many more patent applications. He is a Fellow of the Association for Research in Vision and Ophthalmology (ARVO). Among the awards he has received for his work, Abràmoff received the Young Investigator Award of the Macula Society in 2015 and the Charles D. Phelps Memorial Award for Glaucoma Research in 2016. He is the founder and CEO of IDx, in Coralville, Iowa, a privately held AI company. IDx created the first-ever autonomous AI system authorized by the FDA, which diagnoses disease without human oversight. The IDx-DR system diagnoses diabetic retinopathy in people with diabetes, the primary cause of blindness and visual loss in the United States.
Harold Adams, MD
- Professor, Department of Neurology
Publications
“Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in acute stroke treatment.” Stroke. 1993 Jan;24(1):35-41.
“Guidelines for the early management of adults with ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups: The American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists.” Circulation. 2007 May 22;115(20):e478-534.
Research article summary
The research paper by Dr. Adams and colleagues in Stroke outlines a stroke classification system they established for a multicenter clinical trial of a clot-busting drug known as Org 10172. The researchers aggregated groups of ischemic stroke patients into five broad categories representing the most common causes of ischemic stroke, thereby allowing investigators to report responses to treatment among important subgroups of patients with ischemic stroke. TOAST continues to be an effective tool in stroke studies today.
The Circulation article provides an overview of current evidence about components of the evaluation and treatment of adults with acute ischemic stroke. It includes recommendations for treatment management from the first contact by emergency medical services personnel through initial admission to the hospital.
Dr. Adams is internationally recognized for his expertise and commitment to stroke-related research, patient care, and education. He serves as co-principal investigator of an National Institutes of Health-funded StrokeNet regional coordinating center at Iowa, one of 25 regional centers across the U.S. dedicated to clinical trials and research. Among his numerous awards, Dr. Adams received the A.B. Baker Award for Lifetime Achievement in Neurologic Education from the American Academy of Neurology in 2017.
Nancy C. Andreasen, MD, PhD
- Professor, Department of Psychiatry
- Andrew H. Woods Chair of Psychiatry
- Director, Iowa Neuroimaging Consortium
Publications
“The family history method using diagnostic criteria. Reliability and validity.” Archives of General Psychiatry. 1977. Oct;34(10):1229-35.
“Negative v. positive schizophrenia. Definition and validation.” Archives of General Psychiatry. 1982. July;39(7):789-94.
“Negative symptoms in schizophrenia. Definition and reliability.” Archives of General Psychiatry. 1982. July;39(7):784-8.
“The longitudinal interval follow-up evaluation. A comprehensive method for assessing outcome in prospective longitudinal studies.” Archives of General Psychiatry. 1987 June;44(6):540-8.
Remission in schizophrenia: proposed criteria and rationale for consensus.” American Journal of Psychiatry. 2005 March;162(3):441-9.
Research article summary
Dr. Andreasen is internationally recognized for her research programs in cognitive and affective neuroscience, the genetics and brain mechanisms of psychoses, and the classification of mood disorders. She was a pioneer in the use of neuroimaging techniques; when magnetic resonance imaging became available in the 1980s, she published the first quantitative MR study of brain abnormalities in schizophrenia and bipolar disorder. She and her colleagues also have conducted numerous positron emission tomography studies of aspects of attention, memory, language, emotion, and social cognition.
She led the first modern, empirical study of the relationship between creativity and mental illness. This work was facilitated by her connection to the world-renowned Iowa Writers’ Workshop at the UI. Subsequently, Dr. Andreasen is conducting a second investigation with artists and scientists.
Dr. Andreasen—who earned a medical degree at the UI after serving as an English professor at Iowa for several years—has written acclaimed books for the general public, including The Broken Brain (1985) and Brave New Brain (2004). Among her numerous awards, Dr. Andreasen received the National Medal of Science in 2000 and the National Alliance of Mental Illness Scientific Research Award in 2012. She also is a member of the National Academy of Medicine.
Sue C. Bodine, PhD
- Professor, Department of Internal Medicine—Endocrinology and Metabolism
- Member, Fraternal Order of Eagles Diabetes Research Center
Publications
“Identification of Ubiquitin Ligases Required for Skeletal Muscle Atrophy.” Science. 2001 Nov 23;294(5547):1704-8.
“Akt/mTOR pathway is a crucial regulator of skeletal muscle hypertrophy and can prevent muscle atrophy in vivo.” Nature Cell Biology. 2001 Nov;3(11):1014-9.
Research article summary
In the Science paper, Dr. Bodine and colleagues were the first to use a differential expression analysis to identify two genes that had not previously been identified in skeletal muscle or associated with a decrease in muscle mass. These genes have subsequently been used as important markers of muscle atrophy.
In the Nature Cell Biology paper, Dr. Bodine and colleagues demonstrate for the first time that a protein complex called the mammalian target of rapamycin complex 1 (mTORC1) and its downstream cellular targets were activated under conditions that led to muscle hypertrophy. The team also shows that inhibition of mTOR with rapamycin prevented muscle growth. This study was among the first to examine the role of mTOR in regulating skeletal muscle mass in animal models and humans.
Dr. Bodine’s general field of study is skeletal muscle plasticity. Her current research focuses on identifying the cellular and molecular mechanisms that regulate skeletal muscle mass and determining strategies for preventing muscle mass atrophy or accelerating recovery following a period of muscle loss.
Garry R. Buettner, PhD
- Professor, Department of Radiation Oncology
- Professor, Free Radical and Radiation Biology Program
- Professor, Interdisciplinary Graduate Program in Human Toxicology
- Director, Electron Spin Resonance Facility
Publications
“Spin trapping: ESR parameters of spin adducts.” Free Radic Biol Med. 1987. 3:259-303.
“The pecking order of free radicals and antioxidants: Lipid peroxidation, a‑tocopherol, and ascorbate.” As an Invited Paper, Arch Biochem Biophys. (1993) 300:535‑543.
“Redox state of the cell as viewed though the glutathione disulfide/glutathione couple.” Free Radic Biol Med. (2001) 30:1191-1212.
Research article summary
The three papers Dr. Buettner authored provide essential concepts, tools, and methods for quantitatively observing and measuring free radicals and oxidative stress in biological systems. These tools are critical to scientists’ ability to understand the redox environment of cells and how it influences cellular mechanisms associated with cell growth and development, signaling, and reductive or oxidative stress.
A University of Iowa faculty member since 1993, Dr. Buettner’s research focuses on the basic chemistry and biology of free radicals and related oxidants and antioxidants in human health. His research has been foundational to the new research field of quantitative redox biology, which represents a transition from understanding basic biology of cells and tissues at an observational level to a true mechanistic level. Buettner served as president of the Society for Free Radical Biology and Medicine/Free Radical Research Society from 2004 to 2006 and received the society’s Distinguished Service Award in 2006.
Kevin P. Campbell, PhD
- Professor, Chair, and Departmental Executive Officer, Department of Molecular Physiology and Biophysics
- Professor, Department of Neurology
- Director, Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research Center
- Roy J. and Lucille A. Carver Biomedical Research Chair
- Investigator, Howard Hughes Medical Institute
Publications
“Membrane Organization of the Dystrophin-Glycoprotein Complex.” Cell. 1991 Sep20;66(6):1121-31.
“Primary Structure of Dystrophin-associated Glycoproteins Linking Dystrophin to the Extracellular Matrix.” Nature. 1992 Feb 20;355(63620:696-702.
“A Role for the Dystrophin-Glycoprotein Complex as a Transmembrane Linker Between Laminin and Actin.” Journal of Cell Biology. 1993 Aug;122(4):809-23.
Research article summary
Each of Dr. Campbell’s three papers illuminates a key aspect of the etiology and molecular basis of muscular dystrophy. The Cell manuscript reports on the function of dystrophin, the protein that is absent in Duchenne muscular dystrophy. The Nature article details the discovery of the dystroglycan gene. Building on this observation in his Journal of Cell Biology paper, Dr. Campbell outlines the role of the dystrophin-glycoprotein complex in maintaining muscle-cell integrity.
Collectively, these articles provide a deep understanding of the functions of key proteins involved in muscular dystrophy, and of their interactions with one another, and they serve as a foundation for the development of diagnostic tests and treatment strategies for various forms of the disease.
Dr. Campbell has been a University of Iowa faculty member since 1981, during which he has focused on understanding the molecular, cellular, and physiological basis of various forms of muscular dystrophy and on developing therapeutic strategies to treat these diseases. He is a member of the National Academy of Sciences, the National Academy of Medicine, and the American Academy of Arts and Sciences and has been the recipient of a variety of national and international honors.
Daniel Diekema, MD, MS
- Clinical Professor and Director, Division of Infectious Diseases, Department of Internal Medicine
- Clinical Professor, Department of Pathology
- Associate Hospital Epidemiologist, University of Iowa Hospitals & Clinics
- Associate Director, Clinical Microbiology Laboratory, University of Iowa Hospitals & Clinics
Publication
“Epidemiology of Invasive Candidiasis: A Persistent Public Health Problem.” Clinical Microbiology Reviews. 2007 Jan;20(1):133-63.
Research article summary
Candidiasis is a fungal infection caused by yeasts belonging to the genus Candida. These infections were once considered infrequent and unavoidable complications of health care delivery. Dr. Diekema and colleagues performed numerous studies demonstrating that these infections are common and associated with significant mortality. In this comprehensive review article, Dr. Diekema and co-author Dr. Michael Pfaller argue that invasive Candida infections are an important and underrecognized public health problem in an effort to raise professional awareness and encourage additional work on this important infectious disease.
Dr. Diekema’s areas of expertise include several aspects of health care epidemiology, including the epidemiology of invasive fungal infections in hospitalized patients and the role of the laboratory in preventing infections and controlling antibiotic resistance. He completed fellowships in infectious diseases and medical microbiology, as well as a Master of Science in preventive medicine, at the University of Iowa. He is a past president of the Society for Healthcare Epidemiology of America, and he is a current chair of the Centers for Disease Control and Prevention’s Healthcare Infection Control Practices Advisory Committee.
Michael Edmond, MD, MPH, MPA
- Clinical Professor, Department of Internal Medicine – Infectious Diseases
- Associate Chief Medical Officer, UI Hospitals & Clinics
- Chief Quality Officer, UI Hospitals & Clinics
Publications
“Nosocomial bloodstream infections in United States hospitals: a three-year analysis.” Clinical Infectious Diseases. 1999 Aug;29(2)239-44.
“Nosocomial bloodstream infections in United States hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study.” Clinical Infectious Diseases. 2004 Oct 1;39(7):1093
Research article summary
Nosocomial (hospital-based) bloodstream infections are important causes of morbidity and mortality. For both of Dr. Edmond’s studies published in Clinical Infectious Diseases, Dr. Edmond and colleagues analyze data from 49 U.S. hospitals participating in the SCOPE (Surveillance and Control of Pathogens of Epidemiologic Importance) Project, one of the largest multicenter studies performed at the time.
In the 1999 article, which covers a three-year period (1995-1998), the researchers report more than 10,000 nosocomial infections being detected. The study provides timely data on the epidemiology of these infections and valuable information on emerging trends in antibiotic resistance. In the 2004 study, which reports more than 24,000 cases over a seven-year (1995-2002) period, the researchers find that the proportion of nosocomial bloodstream infections due to antibiotic-resistant organisms is increasing in U.S. hospitals.
Dr. Edmond’s research interests focus on the epidemiology of health care-associated infections and the public policy implications of infection prevention and control. He has published more than 350 research papers, abstracts, and book chapters, and he is a contributor to a the blog Controversies in Hospital Infection Prevention.
Kaikobad Irani, MD
- Professor, Department of Internal Medicine – Cardiovascular Medicine
- Professor, Department of Radiation Oncology
- Professor, Free Radical and Radiation Biology Program
- Member, Fraternal Order of Eagles Diabetes Research Center
Publication
“Mitogenic Signaling Mediated by Oxidants in Ras-Transformed Fibroblasts.” Science. 1997 March 14;275(5306):1649-52.
Research article summary
In the Science paper, Dr. Irani and his research team were among the first to show a link between a common oncogene, cellular free radicals, and unchecked cellular proliferation caused by this oncogene. The paper demonstrates that this oncogene engages a cellular machinery that produces oxygen free radicals, which in turn function as intracellular signals leading to uncontrolled cell division.
Dr. Irani is a physician scientist whose work explores many areas of fundamental cellular and molecular biology. His primary focus is the molecular basis for vascular function and dysfunction in health and disease. His work also extends to questions relating to DNA repair, cancer biology, hemostasis and platelet biology, ischemic injury, myocardial biology, cardiac ion channel function, and whole-body energy utilization and metabolism.
J. Brooks Jackson, MD, MBA
- Vice President for Medical Affairs, University of Iowa
- Dean, UI Carver College of Medicine
- Professor, Department of Pathology
Publication
“Intrapartum and neonatal single-dose nevirapine compared with zidovudine for prevention of mother-to-child transmission of HIV-1 in Kampala, Uganda: HIVNET 012 randomised trial.” The Lancet. 1999 Sep 4;354(9181):795-802.
Research article summary
The research article by Dr. Jackson and colleagues in The Lancet reports on a comparison of two antiviral drugs—nevirapine and zidovudine (AZT)—in HIVinfected pregnant women and their newborn babies in Uganda. The research team found that the nevirapine regimen significantly reduced the risk of maternal-infant transmission of HIV as compared to AZT. Moreover, administration of nevirapine was simpler and considerably less expensive than standard AZT therapy—a significant step in addressing cost barriers and infrastructure challenges to decreasing mother-to-child HIV transmission in developing nations.
A pathologist and internationally recognized AIDS researcher, Dr. Jackson was the principal investigator of the National Institutes of Health–funded International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) Network, which conducted landmark studies of mother-to-child HIV transmission pediatric HIV infection. These trials informed prevention, treatment, and public health policy considerations for children born with HIV worldwide.
Among his administrative leadership roles in academic medicine, Dr. Jackson served as vice president for health sciences and dean of the medical school at the University of Minnesota from 2014-2017. He also served as chair of the pathology department at the Johns Hopkins School of Medicine for 14 years.
Michael Knudson, MD, PhD
- Clinical Professor, Department of Pathology
- Clinical Professor, Department of Radiation Oncology
- Medical Director, Blood Bank and Donor Collections, DeGowin Blood Center, UI Hospitals & Clinics
Publication
“Bax-deficient mice with lymphoid hyperplasia and male germ cell death.” Science. 1995 Oct 6;270(5233):96-9.
Research article summary
This paper describes the consequences of loss of BAX, a heterodimeric and homologous partner of BCL2 with unclear function in vivo. A Bax knockout mouse was generated that proved viable but displayed lineage-specific aberrations in cell death. These results provided strong support for an emerging model at the time that the Bcl-2 family of homologous genes contains both anti-apoptotic and pro-apoptotic family members. The data strongly supported a model that the ratio of these homologous proteins determines a cells susceptibility to apoptotic cell death. This model is now widely accepted and the Bcl-2 family now contains more than a 20 members. Dysregulation of this pathway has subsequently been shown to contribute to a variety of pathological process include neurodegeneration and cancer. Drugs have now been developed and FDA approved to target members of the Bcl-2 family in the treatment of cancer.
Dr. Knudson’s basic research program focused on the role of Bcl-2 family members in cell cycle control and apoptosis, and their role in oncogenesis. He has published more than 30 research papers on this topic. He is the director of the UI Tissue Procurement Core, and he is involved in clinical research in the area of transfusion medicine.
J. Lawrence Marsh, MD
- Professor, Chair, and Departmental Executive Officer, Department of Orthopedics and Rehabilitation
- Director, Orthopedic Residency Program, UI Hospitals & Clinics
- Carroll B. Larson Chair
Publication
“Fracture and dislocation classification compendium – 2007: Orthopaedic Trauma Association classification, database, and outcomes committee.” Journal of Orthopaedic Trauma. 2007 Nov-Dec;21(10 Suppl):S1-133
Research article summary
This new classification compendium republishes the Orthopaedic Trauma Association's (OTA) classification, which was originally published in a compendium of the Journal of Orthopaedic Trauma in 1996. It adopted the Comprehensive Classification of the Long Bones and classified the remaining bones. In this compendium, the introductory chapter reviews new scientific information about classifying fractures that has been published in the previous 11 years. This publication aims to stimulate new developments and interest in a unified language to code and classify fractures.
Dr. Marsh has over 30 years of experience in orthopedic medicine and has been a key leader in developing skills education at the national and regulatory level. His research interests include orthopedic trauma, resident skills education, and orthopedic surgery training and assessment. He also has served as a leader in numerous professional societies. His research and clinical accomplishments have led to appointments as president of the Mid-American Orthopaedic Association, American Orthopaedic Association, and American Board of Orthopaedic Surgery. He has held additional national and regional orthopedic leadership positions, and he has received numerous and extensive research grants related to orthopedic trauma and residency training.
Dawn Quelle, PhD
- Associate Professor, Department of Pharmacology
- Associate Professor, Department of Pathology
- Leader, Cancer Genes and Pathways Program, Holden Comprehensive Cancer Center
Publications
“Overexpression of mouse D-type cyclins accelerates G1 phase in rodent fibroblasts.” Genes & Development. 1993 Aug;7(8):1559-71.
“Alternative Reading Frames of the INK4a Tumor Suppressor Gene Encode Two Unrelated Proteins Capable of Inducing Cell Cycle Arrest.” Cell. 1995 Dec 15;83(6):993-1000.
Research article summary
In the Genes & Development paper, Dr. Quelle provides the first evidence that mammalian D-type cyclins are rate limiting and required for cells to progress through the cell cycle. This work advanced fundamental understanding of cell cycle control in normal cells and abnormal cell proliferation in human diseases, such as cancer. Today, anticancer therapies targeting cyclin D dependent kinases are improving patient survival in the clinic.
Dr. Quelle’s Cell study describes the discovery of the alternative reading frame (ARF) tumor suppressor. It showed that two powerful growth inhibitors, p16 and ARF, are derived from overlapping reading frames within one gene, which is inactivated in almost half of all human cancers. The discovery was also the first time this economical use of multiple reading frames within the same coding sequences had been shown in a mammalian genome.
Dr. Quelle’s research focuses on understanding molecular mechanisms that control cell proliferation and checkpoint responses and how those processes are disrupted during tumor formation. Such knowledge is essential for improving cancer diagnosis, prognosis, and treatment.
Thomas Rutkowski, PhD
- Associate Professor, Department of Anatomy and Cell Biology
Publication
“A trip to the ER: coping with stress.” Trends in Cell Biology. 2004 Jan;14(1):20-8
Research article summary
The accumulation of unfolded proteins in the lumen of the endoplasmic reticulum (ER) induces a coordinated adaptive program called the unfolded protein response (UPR). The UPR alleviates stress by upregulating protein folding and degradation pathways in the ER and inhibiting protein synthesis. With a basic conceptual framework for the UPR, including the identification of key mediators of the response, now in place, recent work has turned towards investigating how the response is regulated and how its effects radiate beyond the immediate realm of protein secretion. In this review article, Dr. Rutkowski highlights advances in these areas.
Dr. Rutkowski’s research seeks to understand a fundamental but poorly understood question in biology: When a cell encounters stress (i.e., anything that perturbs normal cellular function), how does it decide whether to adapt to the stress or die? The Rutkowski laboratory uses diverse experimental approaches to address this question, encompassing systems biology, molecular and cell biology, and vertebrate genetics and physiology. By tackling this question, the team hopes to better understand diseases of stress—including neurodegeneration, cancer, metabolic syndrome, and others, and even normal cellular development and function.
Patrick Schlievert, PhD
- Professor, Chair, and Departmental Executive Officer, Department of Microbiology and Immunology
- Professor, Department of Internal Medicine
- Member, Fraternal Order of Eagles Diabetes Research Center
Publication
“Exotoxins of Staphylococcus aureus,” Clinical Microbiology Reviews. 2000. Jan;13(1):16-34.
Research article summary
The review manuscript is an accumulation of studies by Dr. Schlievert and collaborators describing 21 new infectious diseases caused by a large family of bacterial toxins, known as superantigens. The review addresses the structure and biological functions of the exotoxins and hemolysins secreted by S. aureus. It also addresses the mechanisms of disease causation and efforts to reduce the case/ fatality rate, wherein some of these diseases that once were 100 percent fatal are now fatal in less than one-fourth of cases.
Dr. Schlievert, who earned a BA in general science and a PhD in microbiology at the University of Iowa, is internationally recognized for his studies of superantigens that cause diseases such as toxic shock syndrome and the “flesh-eating disease” caused by S. aureus and Streptococcus pyogenes. Additionally, his laboratory identifies novel strategies to prevent and manage serious human infectious diseases.
Val C. Sheffield, MD, PhD
- Professor and Director, Division of Medical Genetics, Stead Family Department of Pediatrics
- Professor, Department of Ophthalmology and Visual Sciences
- Investigator, University of Iowa Institute for Vision Research
- Director, Interdepartmental Research Program in Human Molecular Genetics
- Roy J. Carver Chair in Molecular Genetics
Publications
“Attachment of a 40-base-pair G+C-rich sequence (GC-clamp) to genomic DNA fragments by the polymerase chain reaction results in improved detection of single-base changes.” Proceedings of the National Academy of Sciences of the United States of America. 1989 Jan;86(1):232-6.
“Identification of a gene that causes primary open angle glaucoma.” Science. 1997 Jan 31;275(5300):668-70.
Research article summary
This paper demonstrates the utility of a novel method for identifying DNA sequence variations to identify genetic disease-causing genes and mutations. This work aided in the identification of numerous human disease-causing genes at a time when DNA sequencing was inefficient and costly. The identification of disease-causing genes has been a major step toward the understanding of the biological mechanisms involved in human genetic diseases.
Dr. Sheffield has spent his entire career at the University of Iowa and is an internationally recognized leader in human molecular genetics and genomics. His lab has identified genes involved in a number of different diseases, including hereditary blindness, congenital heart disease, diabetes, and hypertension, and has played an active role in the human genome project and the rat genome project. Included among his list of honors is the 2018 Lewis Rudin Glaucoma Prize from the New York Academy of Medicine. Dr. Sheffield served as a Howard Hughes Medical Institute investigator for 18 years. He was elected to the National Academy of Medicine in 2005.
Edwin Stone, MD, PhD
- Professor, Department of Ophthalmology and Visual Sciences
- Director, Institute for Vision Research
- Director, Carver Family Center for Macular Degeneration
- Director, Carver Nonprofit Genetic Testing Laboratory
- Seamans-Hauser Chair in Molecular Ophthalmology
Publication
“Identification of a gene that causes primary open angle glaucoma.” Science. 1997 Jan 31;275(5300):668-70.
Research article summary
Glaucoma is characterized by progressive degeneration of the optic nerve and is usually associated with elevated intraocular pressure. Analyses of sequence tagged site (STS) content and haplotype sharing between families affected with chromosome 1q-linked open angle glaucoma were used to prioritize candidate genes for mutation screening. A gene encoding a trabecular meshwork protein, known as the TIGR gene, mapped to the narrowest disease interval by STS content and radiation hybrid mapping. Thirteen glaucoma patients were found to have one of three mutations in this gene (3.9 percent of the population studied). One of these mutations was also found in a control individual (0.2 percent).
In his research, Dr. Stone seeks to understand how small variations in human genes can result in large variations in vision. He and his colleagues focus on identifying and characterizing genes that are involved in three classes of human eye disease: macular degeneration, glaucoma, and heritable photoreceptor degeneration. He also is involved in strategies for bringing new genetic discoveries to the clinic as rapidly as possible; his nonprofit genetic testing laboratory provides low-cost clinical genetic tests for more than 20 different inherited eye diseases on an international scale.
Michael Welsh, MD
- Professor, Department of Internal Medicine-Division of Pulmonary, Critical Care, and Occupational Medicine
- Professor, Department of Molecular Physiology and Biophysics
- Director, Pappajohn Biomedical Institute
- Investigator, Howard Hughes Medical Institute
- Carver Chair in Biomedical Research
- Member, Fraternal Order of Eagles Diabetes Research Center
Publications
“Molecular Mechanisms of CFTR Chloride Channel Dysfunction in Cystic Fibrosis.” Cell. 1993 Jul 2;73(7):1251-4.
“Cellular and Molecular Barriers to Gene Transfer by a Cationic Lipid,” Journal of Biological Chemistry, 1995 Aug 11;270(32): 18997-9007
Research article summary
Building on earlier work that identified disease-causing mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, the Cell manuscript describes how different genetic mutations can “break” the CFTR protein and provides a roadmap for new treatments targeting specific mutant proteins. The JBC paper explores the inefficiency of cationic lipids in gene transfer and provides a framework for new strategies for gene therapy.
Dr. Welsh, who earned BS and MD degrees and completed an internal medicine residency at the University of Iowa, has worked to understand the biology of cystic fibrosis and develop new treatments. He leads a research team that has been awarded more than $90 million in National Institutes of Health funding since 1993. Key to their work is a porcine model of cystic fibrosis, developed with collaborators at the University of Missouri, that is providing a new understanding of the disease and is aiding the development of novel therapies. Dr. Welsh received the 2017 Steven C. Beering Award and the 2018 Warren Alpert Foundation Prize for his cystic fibrosis research.
Joseph Zabner, MD
- Professor and Director, Division of Pulmonary, Critical Care, and Occupational Medicine, Department of Internal Medicine
- Vice Chair for Translational Research, Department of Internal Medicine
Publication
“Cellular and Molecular Barriers to Gene Transfer by a Cationic Lipid.” Journal of Biological Chemistry. 1995 Aug 11;270(32): 18997-9007.
Research article summary
As University of Iowa researchers and others were developing cationic lipids as a vehicle to deliver genes to cells, they learned that this form of gene transfer was inefficient. This paper explores the cellular and molecular bases for the inefficiency and describes several barriers to successful gene transfer and expression. These findings, in turn, informed future efforts for improving gene transfer and eventually developing gene therapy.
Dr. Zabner, who completed a fellowship in pulmonary disease at the University of Iowa, has a research focus on the antibacterial innate immunity of the airway epithelia, in particular how the lack of a chloride channel cystic fibrosis transmembrane conductance regulator (CFTR) results in pulmonary lung infections. A pioneer in gene therapy for cystic fibrosis, Dr. Zabner led the first human trials of gene therapy for cystic fibrosis using a modified adenovirus.