Kittner & Cole Laboratory
Call for appointment:410-328-4323 410-328-4323
The University of Maryland Stroke Research Center’s mission is to better understand stroke etiology and outcomes through epidemiologic and genetic approaches. Our team investigates novel historical, biochemical and genetic risk factors with the goal of developing new strategies to treat and prevent stroke. We perform observational human subject studies at UMMC in collaboration with universities nationwide. Furthermore, we are the coordinating center for a consortium with over 40 investigators from around the world who are dedicated to compiling genetic data and performing international genome-wide association studies in hopes of identifying novel genetic risk loci in early-onset ischemic stroke.
There is a longstanding close collaboration between University of Maryland Stroke Research Center and the Program in Personalized and Genomic Medicine led by Drs. Alan Shuldiner and Braxton Mitchell.
The lab's research focuses on:
- Genetic and environmental risk factors that affect intracerebral hemorrhage
- Genetic and environmental risk factors that affect ischemic stroke with an emphasis on early-onset ischemic stroke
- Genetic and environmental risk factors that influence stroke recovery
Read publications by members of the team on PubMed:
Genetic and Environmental Risk Factors for Hemorrhagic Stroke (GERFHS) and Recovery and Outcomes after Stroke (ROSE)
In collaboration with Dr. Daniel Woo at the University of Cincinnati
Intracerebral hemorrhage (ICH) is a type of stroke that occurs when a blood vessel bursts inside the brain. Every year about 70,000 people have this type of stroke, putting them at risk for severe disability or death. Genetic and Environmental Risk Factors for Hemorrhagic Stroke (GERFHS) is an ongoing case-control study originating from the University of Cincinnati focused on learning more about the environmental factors that affect ICH and identifying genetic risk factors for hemorrhagic stroke, specifically ICH. The goal of this study is to determine changes that lead to disease and develop treatments that may prevent future ICH's from occurring. As a recruitment site, The University of Maryland, actively enrolls research patients from an inpatient setting and coordinates follow ups to assess later outcomes.
GERFHS incorporates a sub study for eligible patients called Recovery and Outcomes after Stroke (ROSE). The ROSE study includes an MRI and additional testing that seeks to better understand the predictors of ICH recovery in addition to the primary goals of GERFHS. The results of this research aim to identify new tests and treatments that will help future generations avoid or recover from this type of stroke.
The Stroke, sTress, RehabilitatiON, and Genetics Study (STRONG)
In collaboration with Dr. Steven Cramer and Dr. Alison Holman at the University of California, Irvine (UCI).
Stroke is the leading cause of long-term disability in Americans. Ischemic stroke, the result of a blockage of blood supply to the brain, makes up about 80% of the types of strokes that occur. Recovery and rehabilitation after ischemic stroke vary widely. While several factors have been identified that influence recovery there is an overall limited basis of knowledge. The STRONG study aims to assess genetic interactions with stress and rehabilitation therapy to better understand recovery after stroke. The University of Maryland, as an active recruitment site for UCI, enrolls subjects from an inpatient setting and coordinates follow ups to assess stress and long-term recovery outcomes.
NINDS International Stroke Genetics Consortium Study (SiGN)
The SiGN study is a funded international collaboration designed to detect genetic variants that predispose to subtypes of ischemic stroke in predominantly older populations. This collaboration includes well-characterized ischemic stroke cases from multiple US and international genetic research centers that have available extensive phenotype data and high-quality DNA. Over the course of this study's lifetime it has produced over 65 papers in scientific journals and is still performing analyses today.
The University of Maryland centrally regulates and archives all available data. Data analysis is performed in a distributed fashion and is available for continued analyses with an internal analytical team who is willing to support worthy projects.
Building off the SiGN network, MRI-GENIE is a funded sub-study that aims to investigate the genetic contribution to acute and chronic stroke burden by combining neuroimaging data with genetic analyses. With contributions from 12 sites worldwide the study team has created an automatic pipeline to extract clinically relevant cerebrovascular MRI traits and perform extensive analyses.
Overall, MRI-GENIE aims to discover genetic determinants of these stroke related MRI traits to identify the underlying genetic architecture of stroke risk and outcomes in acute ischemic stroke.
The Genetics of Early Onset Ischemic Stroke Consortium
The Genetics of Early Onset Ischemic Stroke Consortium is an extension of the international collaboration mentioned above. Early-onset stroke has had few and limited studies done in the past due to difficulty in achieving adequate sample sizes. This consortium has overcome this hurdle because of its longstanding research program in early-onset ischemic stroke and our leadership roles in prior international stroke genetics consortia. This collaboration is taking a two-pronged approach to identifying novel genetic risk loci in early onset-ischemic stroke:
Genetic Susceptibility to Early-Onset Stroke
The aim of this study is to meta-analyze existing genome wide association study (GWAS) data and exome array data in early-onset ischemic stroke to identify common genetic variants as well as rare and low-frequency large-effect exonic variants. An additional aim is to determine whether findings in early-onset stroke are also important for ischemic stroke in older individuals.
Whole Exome Sequencing of Early Onset Ischemic Stroke
This study is an academic/industry partnership with Regeneron Pharmaceuticals. The study will exome sequence samples from early-onset ischemic stroke and controls of the same ancestry from multiple studies world-wide. Exome sequencing is more comprehensive than exome array data and will have a better ability to identify rare variants of large effect size. The goal of this study is to identify genetics findings that could lead to new drug targets or contribute to personalized genomic medicine.
Copy Number Variation and Stroke (CaNVAS)
Large genome-wide association studies (GWAS) of ischemic stroke (IS) populations have been successful at identifying stroke-risk-associated loci with small effect sizes, however, the role of copy number variation (CNV) variation in stroke susceptibility has yet to be explored. We hypothesize that CNV analyses of existing GWAS and exome array data in our assembled data sets of over 24,500 cases and 43,500 controls will be a highly effective and cost-efficient methodology to identify novel associations illuminating stroke mechanisms, treatment targets, and outcome drivers. This project has been submitted to the NIH for funding.
Meet the Stroke Research Team
The UM Stroke Research Center brings together a wide variety of stroke research expertise and offers opportunities for future investigations. With a combined 30+ years of experience in the field, Dr. Steven Kittner and Dr. John Cole have contributed to the current body of knowledge for stroke and stroke genetics and served as mentors to both pre- and post-doctoral trainees. The team also includes a Certified Clinical Research Specialist Tiffany Watson, who has worked with the group for over 10 years, as well as a Senior Research Project coordinator Haley Lopez, BA who has been with the group for 2 years. There is a longstanding, close collaboration between this research group and the Program in Personalized and Genomic Medicine led by Drs. Alan Shuldiner and Braxton Mitchell.
There are participation opportunities in the UM Stroke Research Center for fellows, junior faculty, students, collaborative researchers, etc. Please contact our office for any inquiries.