Research Summary
Dr. Paul Nyquist has an ongoing interest in any translational research project that incorporates well-founded biologic models into patient care in brain injury. He has been involved in a number of clinical trials that have been at the forefront of new technologic innovations in brain injury and has extensive experience in clinical trials in both military and civilian settings. These trials often have involved protocols with high clinical impact on those enrolled.
Dr. Nyquist also has a theoretical focus that emphasizes the role of inflammation in cerebrovascular disease, with particular attention to the effects of inflammation on endothelial activation. He is interested in how inflammation and endothelial activation affect the neurovascular unit. To that end, he is investigating the role of genetic variation on the proclivity of the endothelium to become transformed into a procoagulant state in carotid atherosclerosis.
Using extensive clinical testing for commonly detected risk factors in cerebral vascular disease, Dr. Nyquist is exploring how cerebrovascular small-vessel disease in patients who are predisposed to atherosclerosis may be influenced by inflammation and genetic history. He is also investigating how biomarkers may be used to detect damage in each compartment of the neurovascular unit in the settings of vasospasm and cerebral salt wasting in patients with subarachnoid hemorrhage.
Dr. Nyquist believes that an interrelationship exists between small-vessel disease of the brain and small-vessel disease of the heart and that a number of potential genes may predispose to both. In a study that he conducted in a group of patients who had asymptomatic small-vessel disease of the heart, he found a cross-correlation with silent small-vessel strokes in the brain. His goal is to identify the genes that are associated with cerebral vascular disease in the hopes of developing new treatments for this condition that afflicts millions worldwide.
Clinical Trial Keywords
Intracranial Hemorrhage; Subarachnoid Hemorrhage; Stroke
Selected Publications
View all on PubMed
Extramural Funding
NIH/NINDS RO-1, Funded, Principal Investigator 1R01NS062059-01A1, GRANT00431125, Occult Small Vessel Cerebrovascular Disease in High Risk Families.
Investigator / Inteventional Management of Stroke (IMS) III NIH Sponsored Clinical Trial
Principal Investigator/ Clinical Trial of rFVIIa (Novoseven) in Patients with
Intracerebral Hemorrhage at Johns Hopkins University, Sponsored by NOVONORDISK
Principal Investigator/ Desmotaplase in Acute Stroke at Johns Hopkins University (DIAS), Sponsored by Forest Pharmaceuticals
Investigator, CLEAR, Use of rt-PA for the Resolution of Clot in Intra-
ventricular Hemorrhage, Sponsored by FDA Orphan Drug Program
Investigator / CREST, Carotid Revascularization Endarterectomy vs. Stent Trial, NIH Sponsored Clinical Trial
Principal Investigator/ Siblings with Ischemic Stroke Study Stroke, INOVA Fairfax Hospital
Department of Defense Sponsored Research Projects
Principle Investigator, Project Officer-1993-1996: Complement Levels in Experimental Divers Before and After Dives with a High Predicted Risk of Decompression Sickness.
Project Officer, Principle Investigator -1994-1996: Desmopressin in Submersion Diueresis in Dives of Long Duration.
Project Officer-1995 - 1997: Human Decompression Trial with 1.3 ATA Oxygen in Helium.63713N.M0099.01A.1510.
Medical Monitor-1995 - 1997: Hyperbarcia Recognition and Thermal Status of Exercising Divers Exposed to Cold Water and Elevated PCO2. 63713N.M0099.01B.1428.
Publications:
Vojinovic D, etal..Genome-wide association study of 23,500 individuals identifies 7 loci associated with brain ventricular volume. Nature Communications. 2018 Sep 26;9(1):3945. doi: 10.1038/s41467-018-06234-w.PMID: 30258056
Jian X, et al. Exome Chip Analysis Identifies Low-Frequency and Rare Variants in MRPL38 for White Matter Hyperintensities on Brain Magnetic Resonance Imaging. Stroke. 2018 Jul 12. pii: STROKEAHA.118.020689. doi: 10.1161/STROKEAHA.118.020689.] PMID:30002152
Bulters D, et al. “Haemoglobin scavenging in intracranial bleeding: biology and clinical implications. Nature Reviews Neurology 2018.
Guo S, Lai C, Wu C, Cen G; Alzheimer's Disease Neuroimaging Initiative.Conversion Discriminative Analysis on Mild Cognitive Impairment Using Multiple Cortical Features from MR Images. Front Aging Neurosci. 2017 May 18;9:146. PMID: 28572766
Mackenzie C. Cervenka etal. “A phase I/II multicenter ketogenic diet study for adult super-refractory status epilepticus.” Neurology. 2017 Feb 8. PMID: 28179470
Mohammad Arfan Ikram et al. "Novel genetic loci associated with hippocampal volume" Nature Communications. 2017 Jan 18;8:13624. PMID: 28098162
Adams HH, Hibar DP, Chouraki V, Stein JL, Nyquist PA, Rentería ME, Trompet S, Arias-Vasquez A, Seshadri S, Desrivières S, Beecham AH, Jahanshad N, Wittfeld K, Van der Lee SJ, Abramovic L,….Debette S, Medland SE, Ikram MA, Thompson PM. Novel genetic loci underlying human intracranial volume identified through genome-wide association. Nature Neuroscience. 2016 Oct 3. PMID: 27694991
Franke B, et al.,Genetic influences on schizophrenia and subcortical brain volumes: large-scale proof of concept. Nature Neuroscience. 2016 Mar; 19(3): 420-31. PMID: 26854805
Paul A Nyquist, Murat Bilgel, Rebbecca Gottesman, Lisa R Yanek, Taryn F Moy, Lewis C Becker, Jennifer L Cuzzocreo, Jerry Prince, Bruce A Wasserman, David M Yousem, Diane M Becker, Brian G Kral, Dhananjay Vaidya, “Age Differences in Periventricular and Deep White Matter Lesions.” Neurobiology of Aging. 2015 Jan 7. PMID: 25659858.
Paul A. Nyquist, Lisa r Yanek, Murat Bilgel, Jennifer L Cuzzocreo, Lewis C Becker, Karinne Chevalier-Davis, David Yousem, Jerry Prince, Dhananjay Vaidya, and Diane M Becker, “Effect of White Matter Lesions on Manual Dexterity in Healthy Middle-Aged Persons.” Neurology. 2015 Apr 10. PMID: 25862800
Nyquist PA, Yanek LR, Kral BG, Becker LC, Vaidya D, Becker DM., White Matter Lesion Progression and Cognitive Function Over 5 Years in a Young Susceptible Population. Neuroepidemiology. 2017 Aug 30;49(1-2):62-63. doi: 10.1159/000480238. PMID:28850949
Kral BG, Nyquist P, Vaidya D, Yousem D, Yanek LR, Fishman EK, Becker LC, Becker DM. Relation of Subclinical Coronary Artery Atherosclerosis to Cerebral White Matter Disease in Healthy Subjects From Families With Early-Onset Coronary Artery Disease. Am J Cardiol. 2013 Sep 15; 112(6): 747-52. PMID: 23742943
Nyquist PA, Wang H, Suffredini AF Protein biomarkers in patients with subarachnoid hemorrhage, vasospasm, and delayed ischemic neurological deficits. Acta Neurochir Suppl. 2013; 115:23-5. PMID: 22890638
Murthy SB, Caplan J, Levy AP, Pradilla G, Moradiya Y, Schneider EB, Shalom H, Ziai WC, Tamargo RJ, Nyquist PA, Haptoglobin 2-2 Genotype Is Associated With Cerebral Salt Wasting Syndrome in Aneurysmal Subarachnoid Hemorrhage. Neurosurgery. 2016 Jan; 78(1): 71-6. PMID: 26348010
Nyquist PA, Bilgel MS, Gottesman R, Yanek LR, Moy TF, Becker LC, Cuzzocreo J, Prince J, Yousem DM, Becker DM, Kral BG, Vaidya D, “Extreme Deep White Matter Hyperintensity Volumes Are Associated with African American Race.,” Cerebrovascular Disease, 2014; 37(4): 244-50. PMID: 24686322
Nyquist P, Zhang Z, DeGraba T.”The -928 G/C and -362 G/C Single nucleotide polymorphisms in the promoter of MCP-1: increased transcriptional activity and novel binding sites.” Cerebrovascular Disease 2010 Feb; 29(3): 242-7. PMID: 20029197
Nyquist P,Winkler C, McKenzie L, Yanek L,Becker L,Becker D. “Single nucleotide polymorphisms in monocyte chemoattractant protein-1 and its receptor act synergistically to increase the risk of carotid atherosclerosis.” Cerebrovascular Disease 2009; 28(2): 124-30. PMID: 19506371
Nyquist P, Wityk R, Yanek L, Yousem D, Becker L, Becker D. “High prevalence of silent small vessel cerebrovascular disease and co-occurrence with occult coronary disease in healthy individuals from high risk families.” Neuroepidemiology 2009; 33(1): 66-7. PMID: 19407462
Nyquist P, Ball R, Sheridan MJ “Complement levels before and after dives with a high risk of DCS.” Undersea Hyperb Med. 2007 May-Jun; 34(3): 191-7. PMID: 17672175
Nyquist P, Dick E, Buttolph T. "Detection of leukocyte activation in pigs with neurologic decompression sickness." Aviation Space Environment Medicine. 2004 Mar; 75(3):211-4. PMID: 15018287
