Stroke and Vascular Lab

Our Laboratory of Stroke and Vascular Disease in the Department of Neurosurgery is led by Dr. Petr Tvrdik, PhD. Dr. Tvrdik’s primary research interest is to better understand the molecular underpinnings of neurological disease and use this information to design and implement improved therapies. He has more than twenty years of experience in molecular biology and developmental and functional neuroscience, including a tenure in the Nobel Prize-winning laboratory of Mario Capecchi at the University of Utah. He contributed to several research fields including mitochondrial ATPase assembly, genetics of long chain fatty acid elongases, and the role of Hox genes in brainstem development. More recently, he developed a reporter of intracellular calcium to study calcium activity in the myeloid cells during acute ischemic stroke. Since relocating to the University of Virginia in 2017, Dr. Tvrdik has leveraged that experience and expanded his research in stroke, with particular emphasis on microglia, stroke related neurogenesis and vascular malformations. Dr. Tvrdik completed his PhD in Biochemistry from the Czech Academy of Sciences in Prague, and his postdoctoral training in Molecular Genetics at Stockholm University, Sweden.

The lab also includes post-doctoral research fellow, Dr. Khadijeh Sharifi, PhD, who completed her PhD in Neuroscience from Tehran University, and a team of students and residents, including Jennifer Sokolowski, MD, PhD, Pedro Norat, MD, Jeyan Kumar, MD, Kathryn Kearns, Lei Liu, Sauson Soldozy, Faraz Farzad, Nisha Dabhi and Zeynep Ulutas.

Microglial Calcium Signaling during Ischemic Stroke. We use in vivo imaging of microglial intracellular calcium activity to evaluate signaling responses in microglia during ischemic stroke. before and after blocking calcium channels. NIH Funded.

Cerebral Cavernous Malformations: fundamental mechanisms and experimental treatments. Funding awarded by Focused Ultrasound Foundation, research performed in our pioneering Focused Ultrasound Center.

Role of Wnt-signaling in tissue repair and neurogenesis in the brain after stroke and in aging. Immunohistochemistry, confocal microscopy, and single cell sequencing are employed to elucidate the responses at molecular level. Using Focused Ultrasound to enhance neurogenesis in the aging hippocampus.

Transplantation of Exogenous Mitochondria into the Stroked Brain. Mitochondria are isolated from skeletal muscle and delivered to the stroked brain either by stereotactic injection, or by intraarterial infusion. The outcomes of this intervention are evaluated with histology, immunohistochemical staining, ATP biochemistry, ow cytometry and behavioral assays.

Dynamics of Microglial Phagocytic Activation after Stroke. With intersectional genetic approach, determine how cortical microglia transform to macrophages. Immunohistochemistry and two-photon in vivo imaging is performed to visualize the phagocytic transition in situ. Flow cytometry is used to characterize myeloid cells in the periphery.

Microglial Calcium Waves During the Hyperacute Phase of Ischemic Stroke. Liu L, Kearns KN, Eli I, Sharifi KA, Soldozy S, Carlson EW, Scott KW, Sluzewski MF, Acton ST, Stauderman KA, Kalani MYS, Park M, Tvrdik P. Stroke. 2021 Jan;52(1):274-283. doi: 10.1161/STROKEAHA.120.032766. https://pubmed.ncbi.nlm.nih.gov/33161850/

Calcium Imaging of Microglial Network Activity in Stroke. Tvrdik P, Kearns KN, Sharifi KA, Sluzewski MF, Acton ST, Kalani MYS. Methods Mol Biol. 2019; 2034:267-279. doi: 10.1007/978-1-4939-9658-2_19. https://pubmed.ncbi.nlm.nih.gov/31392691/

In Vivo Imaging of Microglial Calcium Signaling in Brain Inflammation and Injury. Tvrdik P, Kalani MYS.Int J Mol Sci. 2017 Nov 8;18(11):2366. doi: 10.3390/ijms18112366. https://pubmed.ncbi.nlm.nih.gov/29117112/

Intracellular calcium dynamics in cortical microglia responding to focal laser injury in the PC::G5-tdT reporter mouse. Pozner A, Xu B, Palumbos S, Gee JM, Tvrdik P, Capecchi MR. Front Mol Neurosci. 2015 May 8;8:12. doi: 10.3389/fnmol.2015.00012. eCollection 2015. https://pubmed.ncbi.nlm.nih.gov/26005403/

Imaging activity in neurons and glia with a Polr2a-based and cre-dependent GCaMP5G-IRES-tdTomato reporter mouse. Gee JM, Smith NA, Fernandez FR, Economo MN, Brunert D, Rothermel M, Morris SC, Talbot A, Palumbos S, Ichida JM, Shepherd JD, West PJ, Wachowiak M, Capecchi MR, Wilcox KS, White JA, Tvrdik P. Neuron. 2014 Sep 3;83(5):1058-72. doi: 10.1016/j.neuron.2014.07.024. Epub 2014 Aug 21. https://pubmed.ncbi.nlm.nih.gov/25155958/

Mitochondrial dysfunction in neurological disorders: Exploring mitochondrial transplantation. Norat P, Soldozy S, Sokolowski JD, Gorick CM, Kumar JS, Chae Y, Yağmurlu K, Prada F, Walker M, Levitt MR, Price RJ, Tvrdik P, Kalani MYS. NPJ Regen Med. 2020 Nov 23;5(1):22. doi: 10.1038/s41536-020-00107-x. https://pubmed.ncbi.nlm.nih.gov/33298971/

Application of Indocyanine Green Videoangiography in Aneurysm Surgery: Evidence, Techniques, Practical Tips. Norat P, Soldozy S, Elsarrag M, Sokolowski J, Yaǧmurlu K, Park MS, Tvrdik P, Kalani MYS. Front Surg. 2019 Jun 20;6:34. doi: 10.3389/fsurg.2019.00034. eCollection 2019. https://pubmed.ncbi.nlm.nih.gov/31281818/

Fitness Assays Reveal Incomplete Functional Redundancy of the HoxA1 and HoxB1 Paralogs of Mice. Ruff JS, Saffarini RB, Ramoz LL, Morrison LC, Baker S, Laverty SM, Tvrdik P, Potts WK. Genetics. 2015 Oct;201(2):727-36. doi: 10.1534/genetics.115.178079. https://pubmed.ncbi.nlm.nih.gov/26447130/

Nicotinic receptor alpha7 expression identifies a novel hematopoietic progenitor lineage. Gahring LC, Enioutina EY, Myers EJ, Spangrude GJ, Efimova OV, Kelley TW, Tvrdik P, Capecchi MR, Rogers SW. PLoS One. 2013;8(3):e57481. doi: 10.1371/journal.pone.0057481. https://pubmed.ncbi.nlm.nih.gov/23469197/

Prenatal ablation of nicotinic receptor alpha7 cell lineages produces lumbosacral spina bifida the severity of which is modified by choline and nicotine exposure. Rogers SW, Tvrdik P, Capecchi MR, Gahring LC. Am J Med Genet A. 2012 May;158A(5):1135-44. doi: 10.1002/ajmg.a.35372. Epub 2012 Mar 30. https://pubmed.ncbi.nlm.nih.gov/22473653/

Precerebellar cell groups in the hindbrain of the mouse defined by retrograde tracing and correlated with cumulative Wnt1-cre genetic labeling. Fu Y, Tvrdik P, Makki N, Paxinos G, Watson C. Cerebellum. 2011 Sep;10(3):570-84. doi: 10.1007/s12311-011-0266-1. https://pubmed.ncbi.nlm.nih.gov/21479970/

Hematopoietic origin of pathological grooming in Hoxb8 mutant mice. Chen SK, Tvrdik P, Peden E, Cho S, Wu S, Spangrude G, Capecchi MR. Cell. 2010 May 28;141(5):775-85. doi: 10.1016/j.cell.2010.03.055. https://pubmed.ncbi.nlm.nih.gov/20510925/

Reversal of Hox1 gene subfunctionalization in the mouse. Tvrdik P, Capecchi MR. Dev Cell. 2006 Aug;11(2):239-50. doi: 10.1016/j.devcel.2006.06.016. https://pubmed.ncbi.nlm.nih.gov/16890163/

Hoxb1 functions in both motoneurons and in tissues of the periphery to establish and maintain the proper neuronal circuitry. Arenkiel BR, Tvrdik P, Gaufo GO, Capecchi MR. Genes Dev. 2004 Jul 1;18(13):1539-52. doi: 10.1101/gad.1207204. https://pubmed.ncbi.nlm.nih.gov/15198977/

ELOVL2 controls the level of n-6 28:5 and 30:5 fatty acids in testis, a prerequisite for male fertility and sperm maturation in mice. Zadravec D, Tvrdik P, Guillou H, Haslam R, Kobayashi T, Napier JA, Capecchi MR, Jacobsson A. J Lipid Res. 2011 Feb;52(2):245-55. doi: 10.1194/jlr.M011346. https://pubmed.ncbi.nlm.nih.gov/21106902/

ELOVL3 is an important component for early onset of lipid recruitment in brown adipose tissue Westerberg R, Månsson JE, Golozoubova V, Shabalina IG, Backlund EC, Tvrdik P, Retterstøl K, Capecchi MR, Jacobsson A. J Biol Chem. 2006 Feb 24;281(8):4958-68. doi: 10.1074/jbc.M511588200. https://pubmed.ncbi.nlm.nih.gov/16326704/

Role for ELOVL3 and fatty acid chain length in development of hair and skin function. Westerberg R, Tvrdik P, Undén AB, Månsson JE, Norlén L, Jakobsson A, Holleran WH, Elias PM, Asadi A, Flodby P, Toftgård R, Capecchi MR, Jacobsson A. J Biol Chem. 2004 Feb 13;279(7):5621-9. doi: 10.1074/jbc.M310529200. https://pubmed.ncbi.nlm.nih.gov/14581464/

Role of a new mammalian gene family in the biosynthesis of very long chain fatty acids and sphingolipids. Tvrdik P, Westerberg R, Silve S, Asadi A, Jakobsson A, Cannon B, Loison G, Jacobsson A. J Cell Biol. 2000 May 1;149(3):707-18. doi: 10.1083/jcb.149.3.707. https://pubmed.ncbi.nlm.nih.gov/10791983/

The expression of subunit c correlates with and thus may limit the biosynthesis of the mitochondrial F0F1-ATPase in brown adipose tissue. Houstĕk J, Andersson U, Tvrdík P, Nedergaard J, Cannon B.J Biol Chem. 1995 Mar 31;270(13):7689-94. doi: 10.1074/jbc.270.13.7689. https://pubmed.ncbi.nlm.nih.gov/7706317/

Low translational efficiency of the F1-ATPase beta-subunit mRNA largely accounts for the decreased ATPase content in brown adipose tissue mitochondria. Tvrdík P, Kuzela S, Houstĕk J. FEBS Lett. 1992 Nov 16;313(1):23-6. doi: 10.1016/0014-5793(92)81175-l. https://pubmed.ncbi.nlm.nih.gov/1426264/