Michele Calos

Administrative Appointments

• Chair, School of Medicine A&P Committee (2008 - 2010)

Honors and Awards

• Searle Scholar Award, Searle Family Foundation (1983 - 1986)
• Graduate Fellowship, National Science Foundation (1974 - 1979)

Professional Education

Postdoctoral Advisees

I-Ning Wang

Graduate & Fellowship Program Affiliations

• Cancer Biology
• Genetics

Community and International Work

• Member, Board of Directors, American Society of Gene and Cell Therapy 
• Advisory Committee, Food and Drug Administration, Bethesda, Maryland 

Internet Links

• Personal Web site

Industry Relationships

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Current Research Interests

Our research is focused on development of novel vectors and strategies for gene and cell therapy. We want to improve the clinical condition of patients suffering from genetic diseases.

Our primary approach is development of plasmid vectors that integrate at specific sites in the genome. We use the phiC31 phage integrase to mediate sequence-specific genomic integration. We apply this technology to develop innovative therapies for genetic diseases. The two diseases we are focusing on as models are hemophilia and muscular dystrophy.

For hemophilia, we are taking a gene therapy approach. We are trying to create a gene therapy that is simple, safe, effective, and inexpensive and has the potential to be applied worldwide.

Our primary approach involves direct delivery of plasmid DNA to the liver. We inject a plasmid carrying the therapeutic gene for a clotting factor and a plasmid carrying the gene for phiC31 integrase, which will insert the therapeutic gene into the chromosomes.

We have successfully cured mice of hemophilia and are now working with larger animals. We are collaborating with a biopharma company and hope to test our method in clinical trials in the coming years.

To develop a therapy for muscular dystrophy, we are using stem cells. We use phiC31 integrase to insert the therapeutic gene in stem cells derived from the patient. The corrected cells are then transplanted back to the patient, where they can produce intact muscle fibers.

We are currently testing these approaches in mouse models of muscular dystrophy. In one approach, we use stem cells derived from adipose (fat) tissue. In another approach, we make pluripotent stem cells from the patient's adult tissue. In this approach, we employ the sequence-specific integration behavior of phiC31 integrase first to create induced pluripotent stem (iPS) cells, then use integrase to add the therapeutic gene. The corrected cells are ultimately transplanted back to the patient, where they can engraft and generate intact muscle fibers.

If successful, these types of therapies will provide new options for patients suffering from genetic diseases. They will also provide new possibilities for treatment of other common diseases and conditions, including normal aging.

Publications

• Long-Term Expression of Human Coagulation Factor VIII in a Tolerant Mouse Model Using the φC31 Integrase System. Chavez CL, Keravala A, Chu JN, Farruggio AP, Cuéllar VE, Voorberg J, Calos MP. Hum Gene Ther. 2012
• Long-term phenotypic correction in factor IX knockout mice by using phiC31 integrase-mediated gene therapy. Keravala A, Chavez CL, Hu G, Woodard LE, Monahan PE, Calos MP. Gene Ther. 2011; 18 (8): 842-8
• Site-specific recombinase strategy to create induced pluripotent stem cells efficiently with plasmid DNA. Karow M, Chavez CL, Farruggio AP, Geisinger JM, Keravala A, Jung WE, Lan F, Wu JC, Chen-Tsai Y, Calos MP. Stem Cells. 2011; 29 (11): 1696-704
• The therapeutic potential of phiC31 integrase as a gene therapy system. Karow M, Calos MP. Expert Opin Biol Ther. 2011; 11 (10): 1287-96
• Therapeutic applications of the PhiC31 integrase system. Chavez CL, Calos MP. Curr Gene Ther. 2011; 11 (5): 375-81