Hudson Freeze, Ph.D.

Hudson Freeze photo

Hudson Freeze, Ph.D.

Director and Professor

Fax: (858) 795-5381

Lab Website

Hudson Freeze's Research Focus

Congenital Disorders of Glycosylation, Glycosylation-Related Disorders, Crohn’s Disease (Colitis), Cancer

Dr. Freeze’s research focuses on the pathology resulting from faulty glycosylation, the process of adding carbohydrate (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 (CDG). 

Hudson Freeze's Research Report

Glycosylation: An Essential Function

The entire cell surface is coated with sugars in complex chains that promote (or sometimes interfere) with cell-to-cell communication. These sugar chains are first attached to proteins deep inside the cell where they help them get into shape for their jobs. As the proteins percolate toward to cell surface, the sugar chains are sculpted for specific needs. This entire process, called glycosylation, recruits a force of more than 500 genes for this job. The Freeze lab works on several facets of glycosylation, all of them with an eye toward therapeutic applications for diseases that impair the functions of these critical genes. 


 

Human Glycosylation Disorders

Our major focus is on a group of inherited diseases is called Congenital Disorders of Glycosylation (CDG). Today we know of defects in over 125 genes compared to less than 50, only 10 years ago. Patients with these diseases have highly variable mental and motor developmental delay, seizures, failure to grow, hypoglycemia (low blood sugar), clotting and digestion abnormalities, to name just a few. These are rare disorders have over 1,000 known patients worldwide, but it is likely that many remain undiagnosed. Physicians are becoming more aware of glycosylation disorders in general, and basic scientists continue to discover sugar chains at the helm of many basic metabolic processes. Defective glycosylation is also known to cause 15 types of muscular dystrophy. Figure 1 shows the explosive growth in the number of different diseases caused by defective glycosylation. In Figure 2 and the film clip, Harrison Ford poses a few questions for us. Rocket Williams reaches out to us in Figure 3.
 

graph - congenital order of glycosolation
Figure 1


Harrison Ford Knows a lot abuot CDG
Figure 2

The Rocket Fund
Figure 3

The Freeze lab identifies new glycosylation disorders and tries to understand how these defects cause the disease manifestations. Defects occur in genes that activate and transport sugars, assemble them into glycans and remodel them. Some also traffic and distribute the glycosylation machinery within cells. Ongoing collaborations with academic physicians provide a steady flow of new patients for analysis. Since very few laboratories in the United States work on CDG, we are developing new molecular diagnostic methods to handle the increasing number of patients. With the help of generous philanthropic support, we are seeking ways to supplement the depleted glycosylation pathways in patients. 

Hudson Freeze's Bio

Dr. Freeze earned his Ph.D. from the University of California, San Diego in 1976. Subsequently he held fellowships in Biology, Medicine and Neurosciences later joined the faculty at the same institution. In 1988 Dr. Freeze was recruited to Sanford-Burnham Medical Research Institute.


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Publications

A mouse model of a human congenital disorder of glycosylation caused by loss of PMM2.

Chan B, Clasquin M, Smolen GA, Histen G, Powe J, Chen Y, Lin Z, Lu C, Liu Y, Cang Y, Yan Z, Xia Y, Thompson R, Singleton C, Dorsch M, Silverman L, Su SM, Freeze HH, Jin S

Hum Mol Genet 2016 Jun 1 ;25(11):2182-2193

A congenital disorder of deglycosylation: Biochemical characterization of N-glycanase 1 deficiency in patient fibroblasts.

He P, Grotzke JE, Ng BG, Gunel M, Jafar-Nejad H, Cresswell P, Enns GM, Freeze HH

Glycobiology 2015 Aug ;25(8):836-44

The metabolic origins of mannose in glycoproteins.

Ichikawa M, Scott DA, Losfeld ME, Freeze HH

J Biol Chem 2014 Mar 7 ;289(10):6751-61

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Cell-based analysis of CAD variants identifies individuals likely to benefit from uridine therapy.

Del Caño-Ochoa F, Ng BG, Abedalthagafi M, Almannai M, Cohn RD, Costain G, Elpeleg O, Houlden H, Karimiani EG, Liu P, Manzini MC, Maroofian R, Muriello M, Al-Otaibi A, Patel H, Shimon E, Sutton VR, Toosi MB, Wolfe LA, Rosenfeld JA, Freeze HH, Ramón-Maiques S

Genet Med 2020 May 28 ;

Mutations in GET4 disrupt the transmembrane domain recognition complex pathway.

Tambe MA, Ng BG, Shimada S, Wolfe LA, Adams DR, Undiagnosed Diseases Network., Gahl WA, Bamshad MJ, Nickerson DA, University of Washington Centre for Mendelian Genomics., Malicdan MCV, Freeze HH

J Inherit Metab Dis 2020 May 12 ;

Golgi Acidification by NHE7 Regulates Cytosolic pH Homeostasis in Pancreatic Cancer Cells.

Galenkamp KMO, Sosicka P, Jung M, Recouvreux MV, Zhang Y, Moldenhauer MR, Brandi G, Freeze HH, Commisso C

Cancer Discov 2020 Jun ;10(6):822-835

Expanding the molecular and clinical phenotypes of FUT8-CDG.

Ng BG, Dastsooz H, Silawi M, Habibzadeh P, Jahan SB, Fard MAF, Halliday BJ, Raymond K, Ruzhnikov MRZ, Tabatabaei Z, Taghipour-Sheshdeh A, Brimble E, Robertson SP, Faghihi MA, Freeze HH

J Inherit Metab Dis 2020 Feb 12 ;

A Mutation Map for Human Glycoside Hydrolase Genes.

Hansen L, Husein DM, Gericke B, Hansen T, Pedersen O, Tambe MA, Freeze HH, Naim HY, Henrissat B, Wandall HH, Clausen H, Bennett EP

Glycobiology 2020 Feb 10 ;

Defining the clinical phenotype of Saul-Wilson syndrome.

Ferreira CR, Zein WM, Huryn LA, Merker A, Berger SI, Wilson WG, Tiller GE, Wolfe LA, Merideth M, Carvalho DR, Duker AL, Bratke H, Haug MG, Rohena L, Hove HB, Xia ZJ, Ng BG, Freeze HH, Gabriel M, Russi AHS, Brick L, Kozenko M, Earl DL, Tham E, Nishimura G, Phillips JA 3rd, Gahl WA, Hamid R, Jackson AP, Grigelioniene G, Bober MB

Genet Med 2020 May ;22(5):857-866

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