Biomedical Research Education & Training
Faculty Member

Hellerqvist, Carl G., Ph.D.
Professor of Biochemistry, Emeritus

Lab Url: N/A

Phone Number: 615-322-4339

Email Address: carl.g.hellerqvist@vanderbilt.edu

Hellerqvist, Carl's picture
Academic history
M.S., Stockholm University, Sweden
Ph.D., Stockholm University, Sweden
Docent, Stockholm University, Sweden

Office Address   Mailing Address

634 Robinson Research Building

634 RRB 37232-0146


Research Keywords
Pathoangiogenesis, cancer, vaccine and spinal cord injury,Biochemistry,Cancer,Immunology,Microbiology,Neuroscience,Pathology,Receptor,Stem cells,Vascular Biology

Clinical Research Keywords
pathoangiogenesis and cancer

Research Specialty
Identification of an anti-pathoangiogenic agent and its target protein with applications in cancer, RA, ulcers and paralysis.

Research Description
Group B streptococcus (GBS) isolated from human neonates diagnosed with sepsis and respiratory distress produces a polysaccharide exotoxin (CM101), which we have previously described as GBS Toxin. We have recently demonstrated with an ELISA assay that CM101 is present at high concentrations in the plasma and spinal fluid of neonates diagnosed with GBS sepsis. Furthermore, we isolated large quantities of biologically active CM101 from the neonate's urine. We are currently exploring means to block the respiratory distress with direct application to the nursery.

We hypothesized early that CM101 would bind to embryonic receptors in the neonatal lung and would bind to the neovasculature in human tumors. CM101 binds in vivo to the vasculature of human tumors, and in a mouse tumor model causes inflammatory reactions at the tumor site that lead to retarded tumor growth or regression depending on treatment regiment. CM101 treatment, in cancer patients in Phase I clinical trials and in tumor bearing mice over-rides the tumor immunoprivilege, which allows the tumor to grow, and allows inflammatory cells to invade the tumor and induce tumor apoptosis and ablation.

Current research is aimed at an understanding the molecular biology of the anti-pathoangiogenic properties of CM101. We have research interests in several areas:

I. Spinal Cord Injury. CM101 by inhibiting inflammatory angiogenesis prevents secondary inflammatory injury to the spinal cord and scarring. This allows animals to recover from paralysis. CM101 by the same mechanism accelerates wound healing and prevents scar formation. The mechanisms of these events are under investigation.

II. Stem Cell Transplantation in Chronic Spinal Cord Injury. By a mechanism not quite understood, CM101 in picomolar concentration stimulates the differentiation of stem cells into neurons. When these neurons are transferred to the spinal cord cavity created by surgical removal of the gliosis in chronically paralyzed mice, which are treated with i.v. infusions of CM101, the animals show remarkable recovery of motor and sensory function. Functional MRI is being applied to demonstrate the neuronal recovery. The mechanism of CM101 induced differentiation into neurons is under investigation.

III. Clinical and pre-clinical data reveals that the inflammatory response induced by CM101 binding to a target protein in the pathologic vasculature initiates a break down of the immunoprivilege the tumor has created in the host. Leukocyte p53 mRNA is up regulated and tumor apoptosis is induced in p53 negative tumors. The mechanism of this induction remains unsolved.

IV. We have expression cloned the target protein HP59, which CM101 binds to and are addressing the pathophysiology seen in our animal models and in patients in response to CM101 treatment. We have demonstrated by immunohistochemistry that HP59 is uniquely present only in pathologic angiogenesis and aim to develop specific targeting agents for drug development.

V. We have initiated a vaccine program where mice are immunized with HP59-derived peptides. We have attenuated growth of subq implanted tumors by inhibiting angiogenesis and vasculogenesis and i.v. challenges with melanoma cells are not lethal to other immunized mice. These tumor resistant mice have given birth to normal size litter demonstrating that the pathologic and physiologic angiogenesis are distinctly different in expression of HP59.

VI. We are applying our immunization model to better understand the anti-pathoangiogenic properties of CM101 which makes it applicable to rheumatoid arthritis, wound healing, reperfusion injury, spinal cord injury and other diseases driven by pathologic angiogenesis.

Publications
Issued Patent: GBS Toxin Receptor. C.G. Hellerqvist and Changlin Fu. U.S. 6,803,448, Issued October 12, 2004.

Ohlsson, Marcus, Mattsson, Per, Wamil, Barbara D, Hellerqvist, Carl G, Svensson, Mikael. Macrophage stimulation using a group B-streptococcus exotoxin (CM101) leads to axonal regrowth in the injured optic nerve. Restor Neurol Neurosci, 22(1), 33-41, 2004

Issued Patent: Facilitation of Keloid Healing with CM101/GBS Toxin. CG Hellerqvist, M Neeman, BD Wamil and R Abramovitch U.S. 6,569,838 - May 27, 2003.

Issued Patent: Facilitation of Wound Healing with CM101/GBS Toxin. CG Hellerqvist, M Neeman, BD Wamil and R Abramovitch U.S. 6,670,337 - December 30, 2003.

Issued Patent: Facilitation of Repair of Neural Injury with CM101/GBS Toxin. C.G. Hellerqvist, A.W. Wamil and B.D. Wamil. U.S. 6,476,001 - November 5, 2002

Issued Patent: Treatment of Chronic Inflammatory Diseases with CM101/GBS Toxin. C.G. Hellerqvist and B.D. Wamil. U.S. 6,476,002 - November 5, 2002.

Issued patent: Method for purifying GBS toxin/CM101, C.G. Hellerqvist, U.S. 6,407,069, June 18, 2002

Fu, C, Bardhan, S, Cetateanu, N D, Wamil, B D, Wang, Y, Yan, H P, Shi, E, Carter, C, Venkov, C, Yakes, F M, Page, D L, Lloyd, R S, Mernaugh, R L, Hellerqvist, C G. Identification of a novel membrane protein, HP59, with therapeutic potential as a target of tumor angiogenesis. Clin Cancer Res, 7(12), 4182-94, 2001

Nanney, L B, Wamil, B D, Whitsitt, J, Cardwell, N L, Davidson, J M, Yan, H P, Hellerqvist, C G. CM101 stimulates cutaneous wound healing through an anti-angiogenic mechanism. Angiogenesis, 4(1), 61-70, 2001

Issued Patent: Polysaccharide Toxin from Group B b-Hemolytic Streptococcus (GBS) Having Improved Purity. C.G. Hellerqvist. U.S. 6,136,789 - October 24, 2000.

Issued Patent: Treatment of Chronic Inflammatory Diseases with CM101/GBS Toxin. C.G. Hellerqvist and B.D. Wamil. U.S. 6,028,060 - February 22, 2000.

Sundell, H W, Yan, H, Carter, C E, Wamil, B D, Wu, K, Gaddipati, R, Li, D, Hellerqvist, C G. Isolation and identification of the group B streptococcal toxin CM101 from infants with sepsis. J Pediatr, 137(3), 338-44, 2000

Yakes, F M, Wamil, B D, Sun, F, Yan, H P, Carter, C E, Hellerqvist, C G. CM101 treatment overrides tumor-induced immunoprivilege leading to apoptosis. Cancer Res, 60(20), 5740-6, 2000

Issued Patent: Facilitation of Wound Healing with CM101/GBS Toxin. CG Hellerqvist, M Neeman, BD Wamil and R Abramovitch U.S. 5,858,991 - January 12, 1999.

Issued Patent: Methods for Purifying GBS Toxin/CM101. C.G. Hellerqvist U.S. 5,939,396 - August 17, 1999.

Issued Patent: Facilitation of Repair of Neural Injury with CM101/GBS Toxin. C.G. Hellerqvist, A.W. Wamil and B.D. Wamil. U.S. 5,981,508 - November 9, 1999.

Fleischer, A C, Wojcicki, W E, Donnelly, E F, Pickens, D R, Thirsk, G, Thurman, G B, Hellerqvist, C G. Quantified color Doppler sonography of tumor vascularity in an animal model. J Ultrasound Med, 18(8), 547-51, 1999

Issued Patent: Polysaccharide Toxin from Group B b-Hemolytic Streptococcus (GBS) Having Improved Purity. U.S. 5,811,403 - September 22, 1998.

Wamil, A W, Wamil, B D, Hellerqvist, C G. CM101-mediated recovery of walking ability in adult mice paralyzed by spinal cord injury. Proc Natl Acad Sci U S A, 95(22), 13188-93, 1998 PMCID:23754

Yan, H P, Carter, C E, Wang, E Z, Page, D L, Washington, K, Wamil, B D, Yakes, F M, Thurman, G B, Hellerqvist, C G. Functional studies on the anti-pathoangiogenic properties of CM101. Angiogenesis, 2(3), 219-33, 1998

DeVore, R F, Hellerqvist, C G, Wakefield, G B, Wamil, B D, Thurman, G B, Minton, P A, Sundell, H W, Yan, H P, Carter, C E, Wang, Y F, York, G E, Zhang, M H, Johnson, D H. Phase I study of the antineovascularization drug CM101. Clin Cancer Res, 3(3), 365-72, 1997

Hellerqvist, C.G. CM101 - An Anti-Pathoangiogenic Agent: Pre-clinical and Clinical Experiences. NATO/ASI Series - Angiogenesis: Models, Modulators, and Clinical Applications. M.E. Maragoudakis, P.M. Gullino and P.I. Lelkes, Eds. Plenum Press Publishers, New York and London. Series A: Life Sciences, 1997

Wamil, B D, Thurman, G B, Sundell, H W, DeVore, R F, Wakefield, G, Johnson, D H, Wang, Y F, Hellerqvist, C G. Soluble E-selectin in cancer patients as a marker of the therapeutic efficacy of CM101, a tumor-inhibiting anti-neovascularization agent, evaluated in phase I clinical trail. J Cancer Res Clin Oncol, 123(3), 173-9, 1997

Hellerqvist, C G, Lloyd, R S, Wang, E, Bardhan, S. Modulation of interleukin-12 mRNA expression in leukocytes of cancer patients treated with CM101. Ann N Y Acad Sci, 795, 346-8, 1996

Meyerowitz, C B, Fleischer, A C, Pickens, D R, Thurman, G B, Borowsky, A D, Thirsk, G, Hellerqvist, C G. Quantification of tumor vascularity and flow with amplitude color Doppler sonography in an experimental model: preliminary results. J Ultrasound Med, 15(12), 827-33, 1996

Thurman, G B, Page, D L, Wamil, B D, Wilkinson, L E, Kasami, M, Hellerqvist, C G. Acute inflammatory changes in subcutaneous microtumors in the ears of mice induced by intravenous CM101 (GBS toxin). J Cancer Res Clin Oncol, 122(9), 549-53, 1996

Quinn, T E, Thurman, G B, Sundell, A K, Zhang, M, Hellerqvist, C G. CM101, a polysaccharide antitumor agent, does not inhibit wound healing in murine models. J Cancer Res Clin Oncol, 121(4), 253-6, 1995

Sandberg, K., Edberg, K.E., Fish, W., Parker, R., Hellerqvist, C., and Sundell. Thromboxane Receptor Blockage (SQ 29548) in Group B Streptococcal (GBS) Toxin Challenge in Young Lambs. Pediatr. Res., 35, 571-579, 1994

Tamura, M, Harris, T M, Phillips, D, Blair, I A, Wang, Y F, Hellerqvist, C G, Lam, S K, Inagami, T. Identification of two cardiac glycosides as Na(+)-pump inhibitors in rat urine and diet. J Biol Chem, 269(16), 11972-9, 1994

Thurman, G B, Russel, B A, York, G E, Wang, Y F, Page, D L, Sundell, H W, Hellerqvist, C G. Effects of group B Streptococcus toxin on long-term survival of mice bearing transplanted Madison lung tumors. J Cancer Res Clin Oncol, 120(8), 479-84, 1994

Hellerqvist, C G, Thurman, G B, Page, D L, Wang, Y F, Russell, B A, Montgomery, C A, Sundell, H W. Antitumor effects of GBS toxin: a polysaccharide exotoxin from group B beta-hemolytic streptococcus. J Cancer Res Clin Oncol, 120(1-2), 63-70, 1993

Issued Patent: Therapeutic Agent and Method of Inhibiting Vascularization of Tumors. U.S. 5,010,062 - April 23, 1991.

Hellerqvist, C G. Linkage analysis using Lindberg method. Methods Enzymol, 193, 554-73, 1990

Hellerqvist, C G, Sweetman, B J. Mass spectrometry of carbohydrates. Methods Biochem Anal, 34, 91-143, 1990

Pappas, R S, Sweetman, B J, Ray, S, Hellerqvist, C G. Monomer sequence determination of carbohydrates using fast-atom bombardment mass spectrometry of periodate-oxidized acetate ester derivatives. Carbohydr Res, 197, 1-14, 1990

Cumming, D A, Hellerqvist, C G, Harris-Brandts, M, Michnick, S W, Carver, J P, Bendiak, B. Structures of asparagine-linked oligosaccharides of the glycoprotein fetuin having sialic acid linked to N-acetylglucosamine. Biochemistry, 28(15), 6500-12, 1989

Hellerqvist, C G, Sundell, H, Gettins, P. Molecular basis for group B beta-hemolytic streptococcal disease. Proc Natl Acad Sci U S A, 84(1), 51-5, 1987 PMCID:304139

Rojas, J, Palme, C, Ogletree, M L, Hellerqvist, C G, Brigham, K L, Stahlman, M T. Effects of methylprednisolone on the response to group B streptococcal toxin in sheep. Pediatr Res, 18(11), 1141-4, 1984

Murthy, S V, Melly, M A, Harris, T M, Hellerqvist, C G, Hash, J H. The repeating sequence of the capsular polysaccharide of Staphylococcus aureus M. Carbohydr Res, 117, 113-23, 1983

Rojas, J, Larsson, L E, Hellerqvist, C G, Brigham, K L, Gray, M E, Stahlman, M T. Pulmonary hemodynamic and ultrastructural changes associated with Group B streptococcal toxemia in adult sheep and newborn lambs. Pediatr Res, 17(12), 1002-8, 1983

Graber, S E, Hellerqvist, C G. Direct evidence that bacterial lipopolysaccharides elevate cyclic GMP levels in rat fetal liver cells. J Biol Chem, 257(10), 5414-9, 1982

Hellerqvist, C G. Biosynthetic matrices from cells in culture. Methods Enzymol, 82 Pt A, 530-5, 1982

Cumming, D A, Hellerqvist, C G, Touster, O. Identification of a 2-aminotetrose in a lipid-soluble fraction of rat liver. J Biol Chem, 256(15), 7723-6, 1981

Gregg, C R, Melly, M A, Hellerqvist, C G, Coniglio, J G, McGee, Z A. Toxic activity of purified lipopolysaccharide of Neisseria gonorrhoeae for human fallopian tube mucosa. J Infect Dis, 143(3), 432-9, 1981

Hellerqvist, C G, Rojas, J, Green, R S, Sell, S, Sundell, H, Stahlman, M T. Studies on group B beta-hemolytic Streptococcus. I. Isolation and partial characterization of an extracellular toxin. Pediatr Res, 15(6), 892-8, 1981

Krueger, K E, Hellerqvist, C G. Studies on intercellular adhesion. Induction of adhesion by multivalent ligands. J Biol Chem, 256(16), 8553-60, 1981

Krueger, K E, Hellerqvist, C G. Studies on intercellular adhesion. Mechanism of induction of cell adhesion. J Biol Chem, 256(20), 10684-9, 1981

Rojas, J, Green, R S, Hellerqvist, C G, Olegard, R, Brigham, K L, Stahlman, M T. Studies on group B beta-hemolytic Streptococcus. II. Effects on pulmonary hemodynamics and vascular permeability in unanesthetized sheep. Pediatr Res, 15(6), 899-904, 1981

Lindberg, A A, Hellerqvist, C G. Rough mutants of Salmonella typhimurium: immunochemical and structural analysis of lipopolysaccharides from rfaH mutants. J Gen Microbiol, 116(1), 25-32, 1980

Quinn, R W, Lowry, P N, Hellerqvist, C G. Serologic groups of Neisseria gonorrhoeae recovered from patients in Nashville, Tennessee, 1971--1976. Sex Transm Dis, 7(2), 44-8, 1980

Hellerqvist, C G. Intercellular adhesion as a function of the cell cycle traverse. J Cell Biol, 82(3), 682-7, 1979 PMCID:2110494

Schwartz, C E, Hellerqvist, C G, Cunningham, L W. Attaching human fibroblasts secrete a type I procollagen rich in 3-hydroxyproline. Biochem Biophys Res Commun, 90(1), 240-6, 1979

Schwartz, C E, Hoffman, L, Hellerqvist, C G, Cunningham, L W. Scanning electron microscopic visualization of a microexudate prepared by the release of cells by urea. Exp Cell Res, 118(2), 427-30, 1979

Schwartz, C E, Hellerqvist, C G, Cunningham, L W. A collagenous component of the microexudate carpet secreted by attaching human fibroblasts. Ann N Y Acad Sci, 312, 450-2, 1978

Rottmann, W L, Walther, B T, Hellerqvist, C G, Umbreit, J, Roseman, S. A quantitative assay for concanavalin A-mediated cell agglutination. J Biol Chem, 249(2), 373-80, 1974

Hellerqvist, C G, Hoffman, J, Lindberg, A A, Lindberg, B, Svensson, S. Sequence analysis of the polysaccharides from Salmonella newport and Salmonella kentucky. Acta Chem Scand, 26(8), 3282-6, 1972

Hellerqvist, C G, Lindberg, B, Samuelsson, K, Brubaker, R R. Structural studies on the O-specific side-chains of the cell-wall lipopolysaccharide from Pasteurella pseudo-tuberculosis Group II B. Acta Chem Scand, 26(4), 1394-8, 1972

Hellerqvist, C G, Lindberg, B, Samuelsson, K, Brubaker, R R. Structural studies on the O-specific side-chains of the cell-wall lipopolysaccharide from Pasteurella pseudo-tuberculosis Group II A. Acta Chem Scand, 26(4), 1389-93, 1972

Hellerqvist, C G, Rud??n, U, M??kel??, P H. The group C 2 -type modification of the B-type lipopolysaccharide in a hybrid between salmonella groups B and C 2 . Eur J Biochem, 25(1), 96-101, 1972

Lindberg, A A, Holme, T, Hellerqvist, C G, Svensson, S. Studies of a li-hapten isolated from cell-walls of the rough mutant Salmonella typhimurium 395 MR10. Acta Pathol Microbiol Scand [B] Microbiol Immunol, 80(5), 743-50, 1972

Hakomori, S I, Siddiqui, B, Li, Y T, Li, S C, Hellerqvist, C G. Anomeric structure of globoside and ceramide grihexoside of human erythrocytes and hamster fibroblasts. J Biol Chem, 246(7), 2271-7, 1971

Hellerqvist, C G, Hoffman, J, Lindberg, B, Pilotti, A, Lindberg, A A. Anomeric nature of the D-mannose residues in the Salmonella typhi and S. strasbourg lipopolysaccharides. Acta Chem Scand, 25(4), 1512-3, 1971

Hellerqvist, C G, Larm, O, Lindberg, B. Structure of an oligosaccharide obtained on degradation of the lipopolysaccharide from Salmonella typhimurium LT2. Acta Chem Scand, 25(2), 744-5, 1971

Hellerqvist, C G, Lindberg, B, L??nngren, J. Fragmentation anallysis of the salmonella newport lipopolysaccharide. Acta Chem Scand, 25(2), 601-6, 1971

Hellerqvist, C G, Lindberg, B, L??nngren, J, Lindberg, A A. Structural studies on the O-specific side-chains of the cell-wall lipopolysaccharide from Salmonella newington. Acta Chem Scand, 25(3), 939-44, 1971

Hellerqvist, C G, Lindberg, B, Samuelsson, K, Lindberg, A A. Structural studies on the O-specific side-chains of the cell-wall lipopolysaccharide from Salmonella parathyphi A var. durazzo. Acta Chem Scand, 25(3), 955-61, 1971

Lindberg, A A, Hellerqvist, C G. Bacteriophage attachment sites, serological specificity, and chemical composition of the lipopolysaccharides of semirough and rough mutants of Salmonella typhimurium. J Bacteriol, 105(1), 57-64, 1971 PMCID:248321

Nurminen, M, Hellerqvist, C G, Valtonen, V V, M??kel??, P H. The smooth lipopolysaccharide character of 1,4,(5),12 and 1,9,12 transductants formed as hybrids between groups B and D of salmonella. Eur J Biochem, 22(4), 500-5, 1971

Hellerqvist, C G, Lindberg, B, Pilotti, A, Lindberg, A A. Structural studies on the O-specific side-chains of the cell-wall lipopolysaccharide from Salmonella strasbourg. Acta Chem Scand, 24(4), 1168-74, 1970

Lindberg, A A, Holme, T, Hellerqvist, C G, Svensson, S. Bacteriophage receptor development and synthesis of O-specific side chains after addition of D-galactose to the uridine diphosphate-galactose-4-epimeraseless mutant Salmonella typhimurium LT2-M1. J Bacteriol, 102(2), 540-7, 1970 PMCID:247583

Berst, M, Hellerqvist, C G, Lindberg, B, L??deritz, O, Svensson, S, Westphal, O. Structural investigations on T1 lipopolysaccharides. Eur J Biochem, 11(2), 353-9, 1969

Hellerqvist, C G, Larm, O, Lindberg, B, Holme, T, Lindberg, A A. Structural studies on the O-specific side chains of the cell wall lipopolysaccharide from Salmonella bredeney. Acta Chem Scand, 23(7), 2217-22, 1969

Hellerqvist, C G, Lindberg, B, Svensson, S, Holme, T, Lindberg, A A. Structural studies on the O-specific side chains of the cell wall lipopolysaccharides from Salmonella typhi and S. enteritidis. Acta Chem Scand, 23(5), 1588-96, 1969


Postdoctoral Position Available
Yes

Postdoctoral Position Details
Please apply by e-mail to hellercq@ctrvax.vanderbilt.edu sending CV and names of three
references.

Updated Date
10/21/2008