The Genetics Research Center (GRC) was established in 2004 to advance Personalized Medicine and engage the resources of Hartford HealthCare in the development and application of clinical genomics. GRC accelerates the translation of genomics research to improve the quality and safety of patient care.

Genetics Research Center (GRC) at Hartford Hospital

The GRC was established in 2004 under the leadership of Gualberto Ruaño, M.D., Ph.D., to advance Personalized Medicine and engage the resources of the Hartford HealthCare System in the development and application of DNA-guided healthcare. Personalized medicine at Hartford Hospital is an institutional commitment translated to clinical practice. The GRC genomic database and bio-bank includes over 7000 patients in mental illness, diabetes, heart disease, and cancer. GRC has contributed 60 publications to the scientific literature in cardiology, psychiatry, neurobiology, nutrition and metabolism, and population admixture. GRC has been recognized as a national leader in personalized medicine and received $6M of NIH funding.

The GRC has served as incubator for the Genomas Laboratory of Personalized Health (LPH), a CLIA certified pharmacogenetic testing center. To date, more than 5000 patients have been referred to LPH for clinical consultation, which reflects the real time translational component of GRC. LPH has partnered with the clinical laboratory network of Hartford HealthCare, Clinical Laboratory Partners, to bring real-time pharmacogenetic services to clinicians in the state of Connecticut. LPH supports clinical decision through its web-based Personalized Health Portal, which provides interactive guidance on drug selection and dosing based on genotype results and clinical algorithms developed in collaboration with physicians at Hartford Hospital. This Portal has enabled the translation of complex genotype results into clinical practice in the community.

Bedside to Bench: Physiogenomics

GRC operates on the philosophy: Research begins with the patient and ends with the patient. Contrasted to clinical trials or animal experiments, GRC pursues clinical practice as a model system for physiological genomics (physiogenomics) analysis and elevates it to a laboratory for mechanistic inference, a counterpart to animal, cellular, and molecular models of disease. With clinical practice as a model system, GRC accelerates the translation of research findings to personalized healthcare. Using physiogenomics, GRC has already succeeded in utilizing variability in clinical responses to several cardiovascular and neuropsychiatric drugs, to exercise and diets, and to metabolic surgeries and cardiovascular procedures to underscore their common and contrasting mechanisms relevant to efficacy, side effects and disease staging.

Translational medicine is traditionally pursued in the context of translating molecular and cellular models to clinical application, the classical "bench to bedside" paradigm. In physiogenomics, GRC at Hartford Hospital has pursued a combined clinical and genomic approach to learn about mechanism. With clinical practice as a model system, the translation of research findings to personalized healthcare will be accelerated. The scientific benefits are the understanding of the physiological and genetic mechanisms underlying disease and the integration of disease-modifying and pharmacogenetic factors into medical outcomes. The practical clinical benefits are advancement of decision-support systems for personalized health care and the development of genomic diagnostics not only to individualize the diagnosis of disease, but also to manage its treatment according to the innate physiological endowment of each patient.

Gualberto Ruaño, M.D., Ph.D.

Dr. Ruaño is one of the leading medical experts and innovators in personalized healthcare and translational genomics worldwide. He pioneered personalized medicine and has advocated its practice for 25 years. He obtained M.D. and Ph.D. degrees from Yale University. He obtained his B.A. degree from Johns Hopkins University, where he was elected to Phi Beta Kappa. He is Director of Genetics Research at Hartford Hospital and President of Genomas Inc., which he founded in 2004. He holds Adjunct Professorships in the medical faculties at George Washington University and the University of Puerto Rico. He served as founding Senior Editor of the journal Personalized Medicine and was a founding director of the Personalized Medicine Coalition in Washington, D.C. Dr. Ruaño is a Fellow of the National Academy of Clinical Biochemistry and of the American Institute for Medical and Biological Engineering.

Richard Seip, Ph.D.

Dr. Seip is Senior Scientist and Project Manager at the Genetics Research Center. He has co-authored 90 publications in peer-reviewed journals, including recent papers reporting genetic associations with responses to medications, and nutritional, exertional and surgical interventions. Dr. Seip received post-doctoral training in human exercise and lipid metabolic physiology at Washington University School of Medicine in St. Louis from 1990-1992, after having completed a Ph.D. in exercise physiology from the University of Virginia.

 

Research Projects

Patient Population

Research
Projects

Mental Illness

Pharmacogenetics of Psychotropics, Physiogenomics of Functional Brain Imaging

Heart Disease

Pharmacogenetics of Statins and Anti-thrombotics, Physiogenomics of Metabolic Syndrome

Diabetes & Obesity

Physiogenomic Models for Bariatric Surgery, Pharmacogenetics of Oral Hypoglycemics

Cancer

Pharmacogenetics of Tamoxifen, Physiogenomics of Chemotherapy-Induced Neuropathy

Health Disparities

Effects of Genetic Admixture on Clinical Outcomes, Personalized Medicine in Hispanic Population

 

Selected Publications

Date

Selected Publications (linked to PubMed or Publisher)

5/2012

CYP2C19 Genotype-Guided Aniplatelet Therapy in a Patient with Clopidogrel Resistance.
Connecticut Medicine
, 76 (5): 267-272

2/2012

Prediction of Warfarin Dose Reductions in Puerto Rican Patients based on Combinatorial CYP2C9 and VKORC1 Genotypes.
The Annals of Pharmacotherapy
, 46: 208-218

11/2011

Mechanisms of Statin-Induced Myalgia Assessed by Physiogenomic Associations.
Atherosclerosis
, 218 (2):451-456

9/2011

Guidance of Pharmacotherapy in a Complex Psychiatric Case by CYP450 DNA Typing.
Journal of the American Academy of Nurse Practitioners
, 23 (9):459-463

8/2011

Physiogenomic Analysis of CYP450 Drug Metabolism Correlates Dyslipidemia with Pharmacogenetic Functional Status in Psychiatric Patients.
Biomarkers in Medicine
, 5 (4): 439-449

8/2011

Novel Drug Metabolism Indices for Pharmacogenetic Functional Status Based on Combinatory Genotyping of CYP2C9, CYP2C19 and CYP2D6 Genes.
Biomarkers in Medicine
, 5 (4): 427-438

8/2011

Validation of Candidate Genes Associated with Cardiovascular Risk Factors in Psychiatric Patients.
Progress in Neuro-Psychopharmacology & Biological Psych
iatry, 36 (2): 213-219

12/2010

Exposure to Non-Therapeutic INR in a High Risk Cardiovascular Patient: Potential Hazard Reduction with Genotype-Guided Warfarin (Coumadin) Dosing.
Puerto Rico Health Sciences Journal
, 29 (4): 402-408

9/2010

CYP2C9 and VKORC1 genotypes in Puerto Ricans: A case for admixture-matching in clinical pharmacogenetic studies.
Clinica Chimica Acta
, 411: 1306-1311

7/2010

Physiogenomic Analysis of Statin-Treated Patients: Domain Specific Counter Effects within the ACACB Gene on LDL Cholesterol?
Pharmacogenomics
, 11 (7): 959-971

7/2010

Clinical Practice Considerations. In: Laboratory Analysis and Application of Pharmacogenetics to Clinical Practice. Valdes R, Payne D, Linder MW, editors.
The National Academy of Clinical Biochemistry: Laboratory Medicine Practice Guidelines. 23–28

7/2010

Pharmacology and Population Genetics Considerations and Their Applications in Pharmacogenetics. In: Laboratory Analysis and Application of Pharmacogenetics to Clinical Practice. Valdes R, Payne D, Linder MW, editors.
The National Academy of Clinical Biochemistry: Laboratory Medicine Practice Guidelines. 3–10

5/2010

Implementing genotype-guided antithrombotic therapy.
Future Cardiology, 6 (3): 409-424

12/2009

Acetyl-coenzyme A carboxylase alpha gene variations may be associated with the direct effects of some antipsychotics on triglyceride levels.
Schizophrenia Research, 115: 136-140

10/2009

Prevalence of combinatorial CYP2C9 and VKORC1 genotypes in Puerto Ricans: Implications for Warfarin Management in Hispanics.
Ethnicity & Disease, 19: 390-395

9/2009

Bringing DNA-Guided Medicine to the Hispanic Population.
Puerto Rico Health Sciences Journal, 28 (3): 266-267, cover

4/2009

Physiogenomic Analysis of the Puerto Rican Population.
Pharmacogenomics, 10 (4): 565-577

2/2009

Physiogenomic comparison of Edema and BMI in Patients Receiving Rosiglitazone or Pioglitazone.
Clinica Chimica Acta, 400: 48-55

1/2009

Combining fMRI and SNP Data to Investigate Connections Between Brain Function and Genetics Using Parallel ICA.
Human Brain Mapping, 30: 241-255

12/2008

Products for Pharmacogenetic Testing in Psychiatry: A Review of Features and Clinical Realities.
Clinics in Laboratory Medicine, 28: 599-617

11/2008

Increased Carrier Prevalence of Deficient CYP2C9, CYP2C19 and CYP2D6 Alleles in Depressed Patients Referred to a Tertiary Psychiatric Hospital.
Personalized Medicine, 5 (6): 579-587

8/2008

Integrating Genomic Based Information into Clinical Warfarin (Coumadin®) Management: An Illustrative Case Report.
Connecticut Medicine, 72 (7): 399-403

7/2008

DNA Collage and Personalized Medicine.
Connecticut Medicine, 72 (6): 322-cover

6/2008

Physiogenomic Analysis of Localized fMRI Brain Activity in Schizophrenia.
Annals of Biomedical Engineering, 36 (6): 877-88

5/2008

High carrier prevalence of combinatorial CYP2C9 and VKORC1 genotypes affecting warfarin dosing.
Personalized Medicine, 5 (3): 225-232

2/2008

Physiogenomic comparison of human fat loss in response to diets restrictive of carbohydrate or fat.
Nutrition and Metabolism, 5: (1):4

1/2008

Exploring genetic variations that may be associated with the direct effects of some antipsychotics on lipid levels.
Schizophrenia Research, 98: 40-46

11/2007

DNA-guided Decision Support.
Hospital Health Networks, 81 (11): 10

9/2007

Physiogenomic Association of Statin-Related Myalgia to Serotonin Receptors.
Muscle & Nerve, 36: 329-335

5/2007

Physiogenomic Comparison of Weight Profiles of Olanzapine- and Risperidone-Treated Patients.
Molecular Psychiatry, 12: 474- 482

5/2007

A clinical study of the association of antipsychotics with hyperlipidemia.
Schizophrenia Research, 92: 95-102

4/2007

Somatic Complications of Psychotropic Medications in a Patient with Multiple CYP2 Drug Metabolism Deficiencies.
Connecticut Medicine, 71: 197-200

10/2006

Drug-induced metabolic syndrome (DIMS) in psychiatry: a diagnostic need uniquely suited to pharmacogenomics.
American Association for Clinical Chemistry Press, 277-282

5/2006

High carrier prevalence of deficient and null alleles of CYP2 genes in a major USA hospital: Implications for personalized drug safety.
Personalized Medicine, 3 (2): 131-137

5/2006

Physiogenomic analysis of weight loss induced by dietary carbohydrate restriction.
Nutrition and Metabolism, 3: 20-30

4/2006

The Pharmacogenomics of Warfarin (Coumadin) Administration.
Connecticut Medicine, 70 (4): 251-252

3/2006

Physiogenomics: Integrating systems engineering and nanotechnology for personalized health. In: The Biomedical Engineering Handbook, 3rd Edition, Bronzino JD, editor. CRC Press Taylor and Francis, 28: 1-9

3/2006

A common promoter polymorphism of the Apolipoprotein A1 gene affects exercise-induced changes in cholesterol distribution among HDL subfractions.
Atherosclerosis, 185: 65-69

3/2006

Designing Physiogenomic Studies.
Pharmacogenomics, 7(2): 157-158

12/2005

Physiogenomic analysis links serum creatine kinase activities during statin therapy to vascular smooth muscle homeostasis.
Pharmacogenomics, 6 (8): 865-872

8/2005

Personalizing public health.
Personalized Medicine, 2 (3): 239-249

3/2004

Quo Vadis personalized medicine?
Personalized Medicine, 1 (1): 1-7

1/2004

Pharmacogenomic data submission to the FDA: clinical pharmacology case studies.
Pharmacogenomics, 5 (5): 513-517