Sophia Khaldoyanidi

Dr. Khaldoyanidi’s laboratory is focused on the basic biology of stem cells, and on translational aspects of their use for tissue regeneration. The current projects include studies on somatic multipotent stem cells, including hematopoietic stem cells (HSC), mesenchymal stem cells (MSCs), and neural stem cells (NSCs), as well as on pluripotent stem cell (PSC) lines.

The fate of stem cells depends on their interactions with the local microenvironment, i.e. the niche. One of Dr. Khaldoyanidi’s research interests is to identify the cells that contribute to the complex structure of the hematopoietic niche in bone marrow. Her laboratory is also studying the non-cellular compartment of the niche, which includes extracellular matrix molecules, chemokines, anaphylotoxins, and cholinergic mediators. Ongoing studies are investigating the molecular mechanisms by which these factors mediate their effects on the fate of stem cells and on the cross-talk between stem cells and the niche.

Multipotent stem cells, or other differentiated cells derived from pluripotent stem cells, are of potential use for tissue regeneration. One current problem is to generate the desired cells in sufficient quantities for transplantation. The critical issue, which has been insufficiently addressed, is to improve the efficiency of PSC differentiation into the desired specific lineage. Dr. Khaldoyanidi’s laboratory is studying how extracellular matrix components, produced by PSCs, regulate the fate of PSCs.

Transplantation of stem cells is necessary for treatment of many pathological conditions. When cells are administered systemically, the efficiency of transplantation depends on the ability of the stem cells to home to the target organ. Dr. Khaldoyanidi’s laboratory has established a new in vitro method, based on a 3-dimesional (3D) flow chamber device, to investigate the effects of the organ-specific microenvironment on stem cell - endothelial cell interactions under physiological shear stress conditions. The device allows the discrete steps of the cell-cell interaction to be studied, including rolling on, adhesion to, and transmigration of the stem cells across an endothelial layer. This approach will contribute to our understanding of the mechanisms that regulate stem cell migration, and may lead to the development of treatments that either enhance or prevent homing of cells into the target organ.

Education

• 1983-1989:  Medical State University, Novosibirsk, Russian Federation, M.D. (Pediatrics)
• 1989-1993:  Institute of Clinical Immunology, Novosibirsk, Russian Federation, Ph.D. (Immunology/Hematology)
• 2005-2006:  The Burnham Institute for Medical Research, Stem Cell Center, sabbatical; La Jolla, California, USA.

Positions

• 1993-1995:  Guest Scientist, German Cancer Research Center (DKFZ), Heidelberg, Germany.
• 1995-1998:  Guest Scientist, Institute for Genetics (IGEN), Karlsruhe Research Center (FZK), Karlsruhe, Germany
• 1998-1999:  Postdoctoral Fellow, Laboratory for Hematopoiesis Research, Medical Biology Institute, La Jolla, CA, USA
• 1999-2001:  Research Scientist, Department of Vascular Biology, LJIMM, La Jolla, CA, USA
• 2001-2007:  Assistant Professor, Department of Vascular Biology, LJIMM, San Diego, CA, USA
• 2005-2007:  Director, Stem Cells and Regenerative Medicine Program, LJIMM, San Diego, CA, USA
• 2007-Pres :  Associate Member, Torrey Pines Institute for Molecular Studies, San Diego, CA

Professional Affiliations

• American Society of Hematology, since 1998
• International Society of Experimental Hematology, since 2000
• International Society for Hyaluronan Science, Since 2007
• International Society for Stem Cell Research, Since 2008

Honors and Awards

• Medical State University, Novosibirsk, Stipend of Excellence 1983-1989
• Boehrihger Ingelheim, Germany, Guest Scientist Award 1993
• German Cancer Research Center, Heidelberg, Germany, Guest Scientist Award 1994-1995
• Forschungszentrum Karlsruhe, Germany, Guest Scientist Award 1995-1998
• American Society of Hematology, travel Award 1999
• International Society of Hematology, travel Award 2003
• International Drug Discovery Science and Technology, Honorary Member, 2004
• International Society of Hematology, Member of the Month, October 2006

Reviewer:

• Stem Cells
• British Journal of Haematology
• International Journal of Biochemistry and Cell Biology
• International Journal of Biological Macromolecules
• Journal of Immunological Methods
• Oncogen
• PNAS

Editor:

• Frontiers in Bioscience
• Grant reviewer: Universite du Luxemnourg, 2006
• PhM Research Management Group, 2007
• NIH, since 2008.

Selected Publications (10 of 42)

1. Khaldoyanidi, S.K.; Moll, J.; Karakhanova S.S.; Herrlich, P.; Ponta, H. Hyaluronate-enhanced hematopoiesis: Two different receptors trigger the release of interleukin-1beta and interleukin-6 from bone marrow macrophages. Blood (1999), 94(3), 940-949
2. Khaldoyanidi, S., Karakhanova S., Sleeman, J., Herrlich, P., Ponta, H. CD44 variant specific antibodies trigger hemopoiesis by selective release of cytokines from bone marrow macrophages. Blood, (2002),99(11):3955-3961
3. Matrosova V, Orlovskaya I, Serobyan N. and Khaldoyanidi S. Hyaluronic acid facilitates recovery of hematopoiesis impaired by 5-fluouracil administration. Stem Cells, 2004;22:544-555
4. Franz-Josef Mueller, Naira Serobyan, Ingrid U. Schraufstatter, Richard DiScipio, Jeanne F. Loring, Evan Y. Snyder and Sophia K. Khaldoyanidi. Adhesive interactions between human neural stem cells and inflamed human vascular endothelium are mediated by integrins. 2006, Stem Cells, 24(11):2367-72.
5. Irina Orlovskaya, Ingrid Schraufstatter, Jeanne Loring and Sophia Khaldoyanidi. Hematopoietic differentiation of embryonic stem cells. Methods, 2008; 45:159-167
6. Sophia Khaldoyanidi. Directing stem cell homing. 2008, Cell Stem Cell, 2:198-200.
7. Nadezhda Omelyanchuk, Irina A. Orlovskaya, Ingrid U. Schraufstatter  and Sophia K. Khaldoyanidi. Key Players in the Gene Networks Guiding ESCs toward Mesoderm. Journal of Stem Cells, 2009; .4(3):147-160
8. Schraufstatter, I.U., DiScipio, R.G., Zhao, M. and Khaldoyanidi, S.K. C3a and C5a are chemotactic factors for human mesenchymal stem cells, which cause prolonged ERK1/2 phosphorylation. J. Immunol., 2009, 182: 3827-3836.
9. Ingrid Schraufstatter, Naira Serobyan, Richard DiScipio, Natalia Feofanova, Irina Orlovskaya and Sophia Khaldoyanidi. Hyaluronan stimulates mobilization of mature hematopoietic cells but not hematopoietic progenitors. Journal of Stem Cells, 2009:4(4):191-202.
10. Ingrid U. Schraufstatter, Naira Serobyan, Jeanne Loring and Sophia K. Khaldoyanidi. Hyaluronan is required for generation of hematopoietic cells during differentiation of human embryonic stem cells. Journal of Stem Cells, 2010, 14:81-91, 2005.

Patents

• Pending - Device for evaluating in vitro cell migration under flow conditions, and methods of use thereof. United States Patent Application Serial No. 11/395,812. United States Attorney Docket No. 8059-003 PR (filed March 31, 2004)