Vincent C. Hascall, Ph.D.

Staff

Lerner Research Institute
9500 Euclid Avenue
Cleveland, Ohio 44195
Location:ND2-24
hascalv@ccf.org
Phone: (216) 445-5676
Fax: (216) 444-9198



We and our collaborators have shown that cells undergoing stress (viral, endoplasmic reticulum, or hyperglycemic) or injury (wounds) synthesize/deposit an abnormal hyaluronan (HA)-based matrix with structural information that inflammatory cells recognize. We aim to determine: underlying cellular mechanisms that initiate matrix synthesis; internal matrix structures differing from normal HA matrices; and mechanisms whereby inflammatory cells (mast cells, eosinophils, neutrophils, monocytes/macrophages) adhere to and degrade abnormal HA matrix – all key responses in regulation/progression of inflammatory processes.

With our 2011 NIH "Program of Excellence in Glycosciences" award [http://pegnac.sdsc.edu/cleveland-clinic/], we study HA matrix and its interactions with leukocytes in vasculopathies in diabetes, wound healing, inflammatory bowel disease, pulmonary hypertension, and glycocalyx/pericellular matrix modification in vascular development.

We also participate on an NIH-funded project on asthma (S. Erzurum, M.D., PI) using murine airway myofibroblast cultures and a novel organotypic airway epithelium model to determine cellular responses to poly I:C (a viral mimetic) and tunicamycin (endoplasmic reticulum stressor). These two stimuli induce abnormal HA matrices differently. Primary murine mast cells interact with this matrix in early responses to external stresses in lung. Our collaborations continue with M. Aronica, M.D., on the matrix’s role in transgenic mice (TSG-6-null/CD-44-null mice) in the ova/ova challenge asthmatic model; A. Wang on the effect of hyperglycemia in producing this matrix in kidney and bone of streptozotocin-treated diabetic rats; and E. Maytin, M.D., Ph.D., and J. Mack, Ph.D., on how this matrix affects wound healing.

In other words ...

We work to discover how a very large sugar molecule (hyaluronan) interacts with cells that are exposed to viruses, conditions of glucose (sugar) overload, or actual wounds to form an abnormal "matrix" around themselves that attracts certain cells that respond when parts of the body become infected or inflamed. We hope to find what makes the matrix form, how it differs from normal matrix, and how the cells that respond to infection/inflammation get to and interact with the abnormal matrix. With a 2011 NIH Program Project Grant award and other funding, we are studying how the hyaluronan matrix works in the setting of diabetes, wound healing, inflammatory bowel disease, certain cancers, and the lung diseases asthma and pulmonary hypertension.


Amina  Abbadi Ph.D.
Amina Abbadi Ph.D.
Postdoctoral Research Fellow

Location:ND4-18A
Phone:(216) 445-7196
abbadia@ccf.org
Fax:(216) 444-9198
laboratory

Nansy   Albtoush B.S.
Nansy Albtoush B.S.
Graduate Student

Location:ND4-25A
Phone:(216) 445-0421
albtoun@ccf.org
Fax:(216) 444-9198
laboratory

Valbona  Cali
Valbona Cali
Research Technician

Location:ND4-18B
Phone:(216) 444-9369
caliv@ccf.org
Fax:(216) 444-9198
laboratory

Ellie  Lamkin B.S.
Ellie Lamkin B.S.
Research Technician

Location:ND4-25A
Phone:(216) 445-0421
lamkine@ccf.org
Fax:(216) 444-9198
laboratory

Jing Fang  Li M.Eng., MBA
Jing Fang Li M.Eng., MBA
Research Eng Tech II

Location:ND4-18A
Phone:(216) 445-7196
lij3@ccf.org
Fax:(216) 444-9198
laboratory

Jacqueline  Loftis B.S.
Jacqueline Loftis B.S.
Research Engineer

Location:ND4-25A
Phone:(216) 445-0421
loftisj@ccf.org
Fax:(216) 444-9198
laboratory web site

Lisa  MacDowell Mooney
Lisa MacDowell Mooney
Coordinator

Location:ND2-25A
Phone:(216) 445-5088
macdowl@ccf.org
Fax:(216) 444-9198
laboratory

Sergei  Merkoulov Ph.D.
Sergei Merkoulov Ph.D.
Research Associate

Location:ND4-25A
Phone:(216) 445-0421
merkous@ccf.org
Fax:(216) 444-9198
laboratory

Aimin  Wang Ph.D.
Aimin Wang Ph.D.
Staff Scientist

Location:ND4-18B
Phone:(216) 445-3237
wanga@ccf.org
Fax:(216) 444-9198
laboratory


Viola M, Bartolini B, Vigetti D, Karousou E, Moretto P, Deleonibus S, Sawamura T, Wight TN, Hascall VC, De Luca G, Passi A.  Oxidized low density lipoprotein (LDL) affects hyaluronan synthesis in human aortic smooth muscle cells.  J Biol Chem  2013;288:29595-603.  doi: 10.1074/jbc.M113.508341.

Lauer ME, Glant TT, Mikecz K, DeAngelis PL, Haller FM, Husni ME, Hascall VC, Calabro A. Irreversible heavy chain transfer to hyaluronan oligosaccharides by tumor necrosis factor-stimulated gene-6.  J Biol Chem  2013;288:205-14. doi: 10.1074/jbc.M112.403998. PMCID: PMC3537015.

Lauer ME, Cheng G, Swaidani S, Aronica MA, Weigel PH, Hascall VC. Tumor necrosis factor-stimulated gene-6 (TSG-6) amplifies hyaluronan synthesis by airway smooth muscle cells.  J Biol Chem 2013;288:423-31. doi: 10.1074/jbc.M112.389882. PMCID: PMC3537040.

Swaidani S, Cheng G, Lauer ME, Sharma M, Mikecz K, Hascall VC, Aronica MA. TSG-6 protein is crucial for the development of pulmonary hyaluronan deposition, eosinophilia, and airway hyperresponsiveness in a murine model of asthma.  J Biol Chem  2013;288:412-22. doi: 10.1074/jbc.M112.389874. PMCID: PMC3537038.