||Dr. Cucullo joined the Pharmaceutical Sciences faculty in September of 2011. Dr. Cucullo received his doctoral degree in Chemistry and Pharmaceutical Technology from the University of Pisa, (Italy) in 2000. He then continued his education engaging in a postdoctoral training at the Cleveland Clinic in the Dept. of Neurosurgery/Cerebrovascular Research Center where he quickly began specializing in in vitro cerebrovascular modeling and CNS vascular pathophysiology under the guidance of Dr. Damir Janigro, Ph.D.
Prior to joining the School of Pharmacy Dr. Cucullo held the position of Project Scientist in the Dept. of Cell Biology at the Cleveland Clinic and a secondary appointment as Assistant Professor at Case Western Reserve University-Cleveland Clinic Lerner College of Medicine.
In addition to his research and teaching duties Dr. Cucullo serves as Managing Editor for WebMed Central Neurosciences as well as Editorial Board and Lead Faculty in Neuroscience also on WebMed Central. Dr. Cucullo also serves as Associate editor for the journal Oxidants and Antioxidants in Medical Science.
Dr. Cucullo’s research is currently funded by the National Institute of Drug Abuse (R01-DA02912; effects of tobacco smoke toxicity at the blood-brain barrier) and Alternative Research and Development Foundation (effect of hyper- and hypoglycemia on BBB physiology).
Postdoctoral training, Cerebrovascular pathophysiology and BBB modeling, Cerebrovascular Research Center, Cleveland Clinic, 2000 - 2003
Ph.D., University of Pisa, Italy, 2000
Dr. Cucullo research interests are largely focused on translational neuroscience and comprise the following:
1) Cross interactions between the cellular elements of the neurovascular unit
2) Multidrug resistance at the blood-brain barrier
3) Environmental and cellular modulation of blood-brain barrier functions
4) Rheological and pro-inflammatory changes in ischemia and stroke and their role in the pathogenesis of secondary brain injury and neuroinflammation
The current major research effort focuses on unraveling the differential toxicity of standard and “reduced exposure” tobacco products on the BBB and the biological links between cigarette smoke exposure and pathogenesis/progression of CNS disorders. This research encompasses both the study of neuroinflammatory mechanisms and cerebrovascular pathophysiology.
HONORS AND RESEARCH AWARDS
- 2012: NIH Early Career Reviewer Program
- 2012: Alternative Research & Development Foundation Award for the project entitled "Blood-Brain Barrier Damage in Diabetes: Role of Altered Glycemia in the Pathogenesis of CNS Disorders ".
- 2011: 1R01DA029121-01A1 NIH/NIDA Testing tobacco smoke toxicity at the blood-brain barrier
- 2010: Alternative Research & Development Foundation Award for the project entitled "A New Dynamic in vitro Model of the Human Brain Vascular Network ".
- 2008: The Cleveland Clinic Mentor Recognition Award: Science Internship Program.
- 2007: The Cleveland Clinic Mentor Recognition Award: Science Internship Program.
- 2007: Project Award (first place), Cleveland Clinic Foundation, Staff Retreat. “Humanized Dynamic In Vitro Blood Brain Barrier Model: A Convenient Design for Neurovascular Studies”.
- 2007: Invited speaker at the 7th international Conference on Cerebral Vascular Biology (CVB) Ottawa, Canada June 24 – 28.
- 2006: The Cleveland Clinic Mentor Recognition Award: Science Internship Program.
- 2005: Philip Morris External Research Program Award (4 years, $777,350) for the project entitled "A humanized model of the cerebral vasculature to study the effects of smoking on blood-brain barrier endothelial cells".
- 2004: Alternative Research & Development Foundation Award for the project entitled "A new Dynamic in vitro blood-brain barrier model for extensive pharmacological study at the blood-brain barrier".
- 2004: The Cleveland Clinic Innovator Award for the development of “Electrical Stimulation protocols to Inhibit Tumor Cell Proliferation”.
RECENT AND CURRENT FUNDING ( AS PRINCIPAL INVESTIGATOR):
- Alternatives Research and Development Foundation (Cucullo, L. PI) 2012 –2013
Blood-Brain Barrier Damage in Diabetes: Role of Altered Glycemia in the Pathogenesis of CNS Disorders
A hallmark of the chronic complications associated with diabetes mellitus (particularly type 2) is compromised microvascular integrity. The complexity of the processes that cause CNS disease in diabetes and the difficulty of detecting vascular impairments in the large and heterogeneous brain microvascular bed make the study and characterization of this pathology extremely difficult. The main goal of this proposal is to assess the impact and unfold the mechanism/s by which hyper- and hypoglycemia can impair BBB integrity and function.
- 1R01DA029121-01A1 NIH/NIDA (Cucullo, L. PI) 2011 - 2016
Testing tobacco smoke toxicity at the blood-brain barrier
Despite the strong evidence for an association between tobacco smoke and vascular impairment, the impact of TS exposure on the blood-brain barrier (BBB) has been only marginally addressed. The main goal of this proposal is to evaluate the effect of tobacco smoke from reduced-exposure and regular tobacco products on BBB integrity and function. We will also investigate the effect of TS exposure on BBB function and viability in synergism with rheological changes and how this may impact the pathogenesis of secondary brain injury.
- Alternatives Research and Development Foundation (ARDF, 2010 – 2012); A New Dynamic in vitro Model of the Human Brain Vascular Network. The main goal of this proposal was to validate a novel humanized in vitro model of the cerebrovascular system by measuring the pharmacokinetic profile, cell viability, and other distinctive vascular properties of each vascular segment. Role: Principal investigator
- 1R41MH093302-01A2: Development of a BBB Model to Study Transendothelial Cell Migration (2010-2011). Role: Principal investigator of CCF sub-award
- Philip Morris External Research Program (2005-2009). A humanized model of cerebral vasculature to study the effects of smoking on blood-brain barrier endothelial cells. The main goal of this proposal was to investigate of the effects of the exposure to tobacco smoke on BBB integrity and functions. Role: Principal investigator
- Alternative Research Development Foundation (ARDF 2004-2005). Development of a new DIV-BBB for extensive pharmacological study at the BBB. Role: Principal investigator
- S. Oter, S. Jin, L. Cucullo, H.J. Damien Dorman. Oxidants and antioxidants: friends or foes? Oxid Antioxid Med Sci. 2012; 1(1): 1-4
- Naik P, L. Cucullo In vitro blood-brain barrier models: current and perspective technologies. J.Pharm.Sci. 2012 Apr;101(4):1337-54.
- Hossain, P. Mazzone, W. Tierney and L. Cucullo.. In Vitro Assessment of Tobacco Smoke Toxicity at the BBB: Do Antioxidant Supplements Have a Protective Role? BMC Neurosci. 2011 Sep 24;12(1):92
- L. Cucullo, Hossain M., Puvenna V., Marchi N. and Janigro D. The role of shear stress in Blood-Brain Barrier endothelial physiology. BMC Neuroscience 2011 May 11;12:40.
- N. Marchi, A. Johnson4, V. Puvenna, H. L. Johnson, W Tierney, C. Ghosh, L. Cucullo, P.F. Fabene, and D. Janigro. Modulation of peripheral cytotoxic cells and ictogenesis in a model of seizures Epilepsia. 2011 Sep;52(9):1627-34
- L. Cucullo, N. Marchi, M. Hossain and D. Janigro. A Dynamic In vitro BBB model for the study of immune cell trafficking into the CNS. J Cereb Blood Flow Metab. 2011 Feb;31(2):767-77
- P. Mazzone, W. Tierney, M. Hossain, V. Puvenna, D. Janigro and L. Cucullo. Pathophysiological Impact of Cigarette Smoke Exposure on the Cerebrovascular System with a Focus on the Blood-brain Barrier: Expanding the Awareness of Smoking Toxicity in an Underappreciated Area. Int. J. Environ. Res. Public Health (2010)
- Pham N., Fazio V., Cucullo L, Teng Q., Biberthaler P., Bazarian J. and Janigro D. Extracranial Sources of S100B Do Not Affect Serum Levels. PLoS One. 2010 Sep 10;5(9). pii: e12691
- Ghosh C., Gonzalez-Martinez J., Hossain M., Cucullo L., Fazio V., Janigro D., and Marchi N. Pattern of P450 expression at the human blood-brain barrier: Roles of epileptic condition and laminar flow. Epilepsia. 2010 Aug;51(8):1408-17 PM:20074231
- Hossain M., Sathe T., Fazio V., Mazzone P., Weksler B., Janigro D., Rapp E., and Cucullo L. Tobacco smoke: a critical etiological factor for vascular impairment at the blood-brain barrier. Brain Res. (2009) 1287, 192-205. PM:19539613
- Cucullo L., Couraud P.O., Weksler B., Romero I.A., Hossain M., Rapp E., and Janigro D. Immortalized human brain endothelial cells and flow-based vascular modeling: a marriage of convenience for rational neurovascular studies. J. Cereb. Blood Flow Metab (2008) 28, 312-328. PM:17609686
- Cucullo L., Hossain M., Rapp E., Manders T., Marchi N., and Janigro D. Development of a humanized in vitro blood-brain barrier model to screen for brain penetration of antiepileptic drugs. Epilepsia (2007) 48, 505-516. PM:17326793
- Santaguida S., Janigro D., Hossain M., Oby E., Rapp E., and Cucullo L. Side by side comparison between dynamic versus static models of blood-brain barrier in vitro: a permeability study. Brain Res. (2006) 1109, 1-13. PM:16857178
- Janigro D., Perju C., Fazio V., Hallene K., Dini G., Agarwal M.K., and Cucullo L. Alternating current electrical stimulation enhanced chemotherapy: a novel strategy to bypass multidrug resistance in tumor cells. BMC. Cancer (2006) 6, 72. PM:16545134
- Awasthi S., Hallene K.L., Fazio V., Singhal S.S., Cucullo L., Awasthi Y.C., Dini G., and Janigro D. RLIP76, a non-ABC transporter, and drug resistance in epilepsy. BMC. Neurosci. (2005) 6, 61. PM:16188027
- Cucullo L., Dini G., Hallene K.L., Fazio V., Ilkanich E.V., Igboechi C., Kight K.M., Agarwal M.K., Garrity-Moses M., and Janigro D. Very low intensity alternating current decreases cell proliferation. Glia (2005) 51, 65-72. PM:15779084
- Cucullo L., Aumayr B., Rapp E., and Janigro D. Drug delivery and in vitro models of the blood-brain barrier. Curr. Opin. Drug Discov. Devel. (2005) 8, 89-99. PM:15679176
- Marchi N., Hallene K.L., Kight K.M., Cucullo L., Moddel G., Bingaman W., Dini G., Vezzani A., and Janigro D. Significance of MDR1 and multiple drug resistance in refractory human epileptic brain. BMC. Med. (2004) 2, 37. PM:15473912
- Cucullo L., Hallene K., Dini G., Dal Toso R., and Janigro D. Glycerophosphoinositol and dexamethasone improve transendothelial electrical resistance in an in vitro study of the blood-brain barrier. Brain Res. (2004) 997, 147-151. PM:14706866
- Marroni M., Agrawal M.L., Kight K., Hallene K.L., Hossain M., Cucullo L., Signorelli K., Namura S., Bingaman W., and Janigro D. Relationship between expression of multiple drug resistance proteins and p53 tumor suppressor gene proteins in human brain astrocytes. Neuroscience (2003) 121, 605-617. PM:14568021
- Marroni M., Kight K.M., Hossain M., Cucullo L., Desai S.Y., and Janigro D. Dynamic in vitro model of the blood-brain barrier. Gene profiling using cDNA microarray analysis. Methods Mol. Med. (2003) 89, 419-434. PM:12958437
- Krizanac-Bengez L., Kapural M., Parkinson F., Cucullo L., Hossain M., Mayberg M.R., and Janigro D. Effects of transient loss of shear stress on blood-brain barrier endothelium: role of nitric oxide and IL-6. Brain Res. (2003) 977, 239-246. PM:12834884
- Cucullo L., Marchi N., Marroni M., Fazio V., Namura S., and Janigro D. Blood-brain barrier damage induces release of alpha2-macroglobulin. Mol. Cell Proteomics. (2003) 2, 234-241. PM:12714567
- Marroni M., Marchi N., Cucullo L., Abbott N.J., Signorelli K., and Janigro D. Vascular and parenchymal mechanisms in multiple drug resistance: a lesson from human epilepsy. Curr. Drug Targets (2003).4,297-304. PM:12699350
- Marchi N., Fazio V., Cucullo L., Kight K., Masaryk T., Barnett G., Vogelbaum M., Kinter M., Rasmussen P., Mayberg M.R., and Janigro D. Serum transthyretin monomer as a possible marker of blood-to-CSF barrier disruption. J. Neurosci. (2003) 23, 1949-1955. PM:12629200
- Cucullo L., McAllister M.S., Kight K., Krizanac-Bengez L., Marroni M., Mayberg M.R., Stanness K.A., and Janigro D. A new dynamic in vitro model for the multidimensional study of astrocyte-endothelial cell interactions at the blood-brain barrier. Brain Res. (2002) 951, 243-254. PM:12270503
- Desai S.Y., Marroni M., Cucullo L., Krizanac-Bengez L., Mayberg M.R., Hossain M.T., Grant G.G., and Janigro D. Mechanisms of endothelial survival under shear stress. Endothelium (2002) 9, 89-102. PM:12200960
- Dombrowski S.M., Desai S.Y., Marroni M., Cucullo L., Goodrich K., Bingaman W., Mayberg M.R., Bengez L., and Janigro D. Overexpression of multiple drug resistance genes in endothelial cells from patients with refractory epilepsy. Epilepsia (2001) 42, 1501-1506. PM:11879359
- Naik P., Prasad S., Cucullo L. “Role and Function of Dehydrogenases in Blood-Brain Barrier Physiology and CNS disorders” in Dehydrogenases. In Tech, 2012, ISBN 978-953-307-019-3.
- Cucullo L., Marchi N., Fazio V., Nguyen M., and Janigro D. “Blood-brain barrier, blood flow and Neoplasms: the role of astrocytes” in Epilepsy: Mechanisms, Models, and Translational Perspectives. CRC-press, June 2010. ISBN: 978-1-4200855-9-4
- Cucullo L. “Prenatal development of the human BBB”, in Mammalian Brain Development, D. Janigro Editor, Humana Press, (Totowa,NJ) 2009; 53-75. ISBN 978-1-60761-286-5
- Cucullo L., Oby E., Hallene K., Aumayr B., Rapp ED., AND Janigro D. Artificial blood-brain barrier in Dermietzel, Spray, Nedergaard (Eds): Blood-Brain Interfaces-From Ontogeny to Artificial Barriers, February 2006. ISBN 3-527-31088-6 - Wiley-VCH, Weinheim.
- Cucullo L. “Vascular differentiation and cell cycle”, in Cell Cycle in the Central Nervous System, D. Janigro Editor, Humana Press, (Totowa, NJ) 2006; 319-329. ISBN 1-58829-529-X
ABSTRACTS AND PRESENTATIONS:
Total includes more than 85 from local, national and international meetings