ABOUT DR. FREEZE and HIS RESEARCH

Dr.  Freeze joined  the  faculty  at  the  Sanford  Burnham  Institute  in  1988  and  served  as  the Director of the Glycobiology and  Carbohydrate Chemistry Program  from 2000-2008.   His work focuses on pathology resulting from faulty glycosylation, the process of adding sugar chains to proteins  and  lipids. Carbohydrates are required for proper secretion and targeting of thousands of proteins an often overlooked fact of biology.

He is driven by the search for novel therapeutics to treat patients with mutations leading to glycosylation defects called Congenital Disorders of Glycosylation or CDGs.  We invite you to learn about the children with CDGs, read their stories, and meet the researchers seeking a cure for their disorders.

RESEARCH FOCUS

CONGENITAL DISORDERS OF GLYCOSYLATION (CDG)

Today we know of defects in over 35 genes for CDGs compared to just 3 a decade ago. Patients with these diseases have highly variable mental and motor retardation, seizures, failure to grow, hypoglycemia (low blood sugar), clotting and digestion abnormalities, to name just a few.  There are less than 1000 known patients worldwide, but it is likely that there are many more who remain undiagnosed. Physicians are becoming more aware of CDG and glycosylation in general, and basic scientists continue to discover sugar chains at the helm of many basic metabolic processes. To learn more about our research into these disorders click here.

PROTEIN-LOSING ENTEROPATHY (PLE)

Another major interest in the lab is PLE, where blood proteins leak through the intestine, causing massive fluid imbalance. Some types of CDG patients experience this, but so do and children who have had a Fontan surgery to correct their congenital heart defects. A few percent of these children sometimes develop PLE months to years after their surgery. Its basis, and why PLE strikes only certain children is a mystery.  Aided by the Children’s Hearts Fund, March of Dimes Foundation and the NIH, the lab has focused on understanding how key molecules and environmental insults interact to drive PLE. To learn more about our research into these disorders click here. 

INFLAMMATION, CANCER, CROHN’S AND COLITIS

Another interest in the lab is how an unusual glycan modification is involved in inflammation including Crohn’s disease, ulcerative colitis, and cancer. A monoclonal antibody against this unusual sugar chain modification, called a “carboxylate”, showed encouraging signs as a potential therapy for inflammatory-related diseases.  A limited number of proteins carry this “carboxylate” modification and many are known to be involved in cell apoptosis or the development of inflammatory disorders. Recent results show therapeutic promise because the antibody can slow tumor growth. Dr. Geetha Srikrishna is the driving force behind this exciting project.To learn more about our research into these disorders click here.