Ellen Heber-Katz

Ellen Heber-Katz, PhD
Born Philadelphia, Pennsylvania
Fields Immunology, Microbiology
Institutions Lankenau Institute for Medical Research
The Wistar Institute
Alma mater University of Pennsylvania (PhD)
University of Wisconsin–Madison (BA)(MS)
Notable awards National Institutes of Health Eureka Grant
National Cancer Institute’s Director’s Provocative Question Initiative Grant

Ellen Heber-Katz, PhD, is a professor at Lankenau Institute for Medical Research (LIMR), a biomedical research facility in Wynnewood, Pa., a suburb of Philadelphia.[1] She is an immunologist who investigates mammalian regeneration,[2][3][4][5][6] having discovered the unusual ability of the MRL mouse strain (used in autoimmunity research) to regenerate wounds without scarring and to fully restore damaged tissues, an ability not normally seen in mammals. Her work on regeneration has been extended into National Cancer Institute (NCI)-funded studies of novel aspects of breast cancer causation.[7] Her research interests include immunology, regenerative medicine and cancer.[8]

Education and career

Dr. Heber-Katz earned her B.A. in microbiology and immunology from the University of Wisconsin-Madison, in 1969, and her M.S. in immunology from the same university in 1972.[9] For her M.S. thesis, she studied the role of reducing agents as a critical factor in cellular immune responses.[10] She then moved to Philadelphia to attend the University of Pennsylvania and was awarded her Ph.D. in immunology in 1976. For her doctoral thesis she demonstrated that single T-cell subsets could respond to both histocompatibility antigens and environmental antigens, establishing the unity of these two branches of the immune response.[11] She continued that theme as a postdoctoral fellow at the National Institutes of Allergy and Infectious Diseases in the Laboratory of Immunology (part of the National Institutes of Health [NIH]) with the first functional evidence for the T cell–antigen-MHC-Ia tri-molecular complex anticipating the crystal structure. It had long been known that T cells could be activated against foreign antigens (e.g., viruses, bacteria) only when these were "presented" to the T cell by specialized cells known as macrophages. What was not known was how the cells made their critical interactions.

With a very clever use of genetically inbred mice, Dr. Heber-Katz and collaborators dissected the fine molecular details that control the T-cell and macrophage interaction. This well-known "A/5R experiment" confirmed the Determinant Selection Hypothesis concerning the spatial relationships between the histocompatibility I-A and I-E molecules on the surface of antigen- presenting cells, the bound antigen and the recognition structure of the T-cell receptor. That "tri-molecular complex" is the fundamental unit of specificity in the immune response.[12]

Immunology studies

Upon leaving the NIH, Dr. Heber-Katz was recruited to the Wistar Institute, Philadelphia, by its director and famed vaccinologist Hilary Koprowski, MD. While at Wistar, Dr. Heber-Katz developed the first vaccine capable of eliciting a purely T-cell response that was fully protective against a lethal challenge of herpes simplex virus in the complete absence of antibodies, and she patented a generic structure for a purely T-cell activating vaccine.[13] That T cells alone — in the absence of a detectable antibody response — could confer protection against a lethal viral challenge was outside of mainstream thinking at the time (mid-1980s). Today, it is recognized as a critical vaccine concept.

Broadening her immunology studies into the area of autoimmunity, she discovered that particular autoimmune diseases were under the control of delimited and separable T-cell receptor subsets (the V-region disease hypothesis).[14] It was during the course of an autoimmunity study that Heber-Katz discovered the regeneration trait of the MRL mouse,[15][16][17] which has largely occupied her research program for the past 15 years.

In 2014, Dr. Heber-Katz brought her lab to LIMR, which is part of Main Line Health, a non-profit health system serving portions of Philadelphia and its surrounding suburbs.[18] She also is a member of the Molecular Biology and Genetics Program at the Sidney Kimmel Cancer Center at Thomas Jefferson University. She holds five patents for vaccines and wound healing.

Mammalian regeneration

While working at the Wistar Institute in 1996, Dr. Heber-Katz serendipitously discovered the unusual ability of the MRL mouse strain (which had been used for almost 50 years in autoimmunity research) to regenerate wounds without scarring and to fully restore damaged tissues, including cartilage and hair follicles, an ability not normally seen in mammals. It had long been assumed that amphibians and reptiles were the last branch of the evolutionary tree capable of regenerating lost or injured tissues, organs and limbs, while mammals (including mice and humans) were, with a few rare exceptions, capable only of tissue repair (scarring). Dr. Heber-Katz's discovery of the "super-healer" MRL mouse initiated the study of multi-organ/multi-tissue regeneration beyond amphibian biology to a medically significant species of mammal.[19][20][21][22][23][24][25][26][27][28][29][30] Her bold move into this field led to her worldwide recognition as thought leader in the field of regenerative biology.[31][32] In particular, Dr. Heber-Katz initiated extensive collaborations that helped pioneer the genetics of regenerative wound healing, gene expression patterns, the role of immune and inflammatory responses, and a unique metabolic state (aerobic glycolysis) reminiscent of developing embryos. Over the years, her research has extended to multiple tissue types including cartilage, cardiac and nerve regeneration. In 2010, the Heber-Katz laboratory showed that the deletion of a single gene, p21cip/waf, involved in cell cycle regulation, could confer the regeneration trait in otherwise non–regeneration-competent mice.

In 2015, Dr. Heber-Katz demonstrated that the hypoxia response pathway regulated by HIF1a (hypoxia inducible factor) is the central regulator of regeneration. Importantly, using a drug construct (1,4DPCA/hydrogel) to up-regulate HIF1a protein converted non-regenerating mouse strains into super-healers like the MRL. This finding has moved basic studies into a translational direction. Her ground-breaking work continues to be supported by multiple grants from several branches of the National Institutes of Health, including a Eureka grant from National Institute of Dental and Craniofacial Research, and a Provocative Question Director’s award from NCI, as well as previous funding from private foundations and from the Defense Advanced Research Projects Agency of the U.S. Department of Defense.

References

  1. ↑ "Ellen Heber-Katz, PhD - LIMR - Researcher Profile". LIMR. Retrieved 2016-04-02.
  2. ↑ "Tendon regeneration and scar formation: The concept of scarless healing". Journal of Orthopaedic Research. 33: 823–831. doi:10.1002/jor.22853. Retrieved 2016-04-02.
  3. ↑ Zhang, Yong (2015-06-03). "Drug-induced regeneration in adult mice | Science Translational Medicine". Stm.sciencemag.org. Retrieved 2016-04-02.
  4. ↑ Gourevitch, D; Kossenkov, AV; Zhang, Y; Clark, L; Chang, C; Showe, LC; Heber-Katz, E (2015-09-28). "Inflammation and Its Correlates in Regenerative Wound Healing: An Alternate Perspective". Adv Wound Care (New Rochelle). 3: 592–603. doi:10.1089/wound.2014.0528. PMC 4152783Freely accessible. PMID 25207202.
  5. ↑ Edwards, RG (2015-09-28). "From embryonic stem cells to blastema and MRL mice". Reprod. Biomed. Online. 16: 425–61. PMID 18339268.
  6. ↑ "Case Closed: A Fluky Finding Raises Hopes for Mending Wounds". Scientific American. Retrieved 2016-04-02.
  7. ↑ Nathan A. Berger. "Murine Models, Energy Balance, and Cancer: 9783319167329: Medicine & Health Science Books @". Amazon.com. Retrieved 2016-04-02.
  8. ↑ "From Immunity and Vaccines to Mammalian Regeneration". The Journal of Infectious Diseases. 212. 2015. Retrieved 2016-04-03.
  9. ↑ "http://www.limr.org/lmr/Page.asp?out=html&searchType=Faculty&PageID=LMR000321"
  10. ↑ Click, RE (2015-09-28). "A review: alteration of in vitro reproduction processes by thiols —Emphasis on 2-mercaptoethanol". J. Reprod. Dev. 60: 399–405. doi:10.1262/jrd.2014-055. PMC 4284312Freely accessible. PMID 25087867.
  11. ↑ D. B. Wilson; E. Heber-Katz; J. Sprent; J. C. Howard* (1977-01-01). "On the Possibility of Multiple T-cell Receptors". Symposium.cshlp.org. Retrieved 2016-04-02.
  12. ↑ Heber-Katz, E; Hansburg, D; Schwartz, RH (2015-09-28). "The Ia molecule of the antigen-presenting cell plays a critical role in immune response gene regulation of T cell activation.". J. Mol. Cell. Immunol. 1: 3–18. PMID 6101061.
  13. ↑ "Patent US5837249 - Method for generating an immunogenic T cell response protective against a virus - Google Patents". Google.com. Retrieved 2016-04-02.
  14. ↑ Heber-Katz, E; Acha-Orbea, H (2015-09-28). "The V-region disease hypothesis: evidence from autoimmune encephalomyelitis.". Immunol. Today. 10: 164–9. doi:10.1016/0167-5699(89)90174-6. PMID 2663017.
  15. ↑ Lise Desquenne Clark; Robert K. Clark; Ellen Heber-Katz (July 1998). "A New Murine Model for Mammalian Wound Repair and Regeneration" (PDF). Clinical Immunology and Immunopathology. 88: 33–45. Retrieved 2016-04-03.
  16. ↑ Morelle, Rebecca (2006-04-11). "Science/Nature | Mouse sheds light on regeneration". BBC News. Retrieved 2016-04-02.
  17. ↑ "The super super-healing MRL mouse strain". Frontiers in Biology. 7: 522–538. doi:10.1007/s11515-012-1192-4.
  18. ↑ "Archived copy". Archived from the original on March 6, 2016. Retrieved March 30, 2016.
  19. ↑ "Heredity - Fine-mapping quantitative trait loci affecting murine external ear tissue regeneration in the LG/J by SM/J advanced intercross line". Heredity. 112: 508–518. doi:10.1038/hdy.2013.133.
  20. ↑ "ARTICLES | Physiological Genomics". Physiolgenomics.physiology.org. 2013-06-01. Retrieved 2016-04-02.
  21. ↑ Heber-Katz, E; Zhang, Y; Bedelbaeva, K; Song, F; Chen, X; Stocum, DL (2015-09-28). "Cell cycle regulation and regeneration". Curr. Top. Microbiol. Immunol. 367: 253–76. doi:10.1007/82_2012_294. PMID 23263201.
  22. ↑ "Heritability of articular cartilage regeneration and its association with ear wound healing in mice". Arthritis & Rheumatism. 64: 2300–2310. 2012-01-24. doi:10.1002/art.34396. Retrieved 2016-04-02.
  23. ↑ Arthur, LM; Heber-Katz, E (2015-09-28). "The role of p21 in regulating mammalian regeneration". Stem Cell Res Ther. 2: 30. doi:10.1186/scrt71. PMC 3152998Freely accessible. PMID 21722344.
  24. ↑ Vorotnikova, E; McIntosh, D; Dewilde, A; Zhang, J; Reing, JE; Zhang, L; Cordero, K; Bedelbaeva, K; Gourevitch, D; Heber-Katz, E; Badylak, SF; Braunhut, SJ (2015-09-28). "Extracellular matrix-derived products modulate endothelial and progenitor cell migration and proliferation in vitro and stimulate regenerative healing in vivo". Matrix Biol. 29: 690–700. doi:10.1016/j.matbio.2010.08.007. PMID 20797438.
  25. ↑ Bedelbaeva, K; Snyder, A; Gourevitch, D; et al. (March 2010). "Lack of p21 expression links cell cycle control and appendage regeneration in mice". Proceedings of the National Academy of Sciences. 107: 5845–5850. doi:10.1073/pnas.1000830107. PMC 2851923Freely accessible. PMID 20231440. Retrieved 2016-04-03.
  26. ↑ Naviaux, RK; Le, TP; Bedelbaeva, K; Leferovich, J; Gourevitch, D; Sachadyn, P; Zhang, XM; Clark, L; Heber-Katz, E (2015-09-28). "Retained Features of Embryonic Metabolism in the Adult MRL Mouse". Mol. Genet. Metab. 96: 133–44. doi:10.1016/j.ymgme.2008.11.164. PMC 3646557Freely accessible. PMID 19131261.
  27. ↑ Ellen Heber-Katz; John Leferovich; Khamilia Bedelbaeva; Dmitri Gourevitch; Lise Clark (2004). "The scarless heart and the MRL mouse" (PDF). The Royal Society. 359: 785–93. doi:10.1098/rstb.2004.1468. PMC 1693365Freely accessible. PMID 15293806. Retrieved 2016-04-03.
  28. ↑ "Sexually dimorphic genes regulate healing and regeneration in MRL mice". Mammalian Genome. 14: 250–260. doi:10.1007/s00335-002-2222-3. Retrieved 2016-04-03.
  29. ↑ "Matrix metalloproteinase activity correlates with blastema formation in the regenerating MRL mouse ear hole model". Developmental Dynamics. 226: 377–387. 2003-01-14. doi:10.1002/dvdy.10243. Retrieved 2016-04-03.
  30. ↑ "Regeneration: Stem Cells and Beyond | Ellen Heber-Katz". Springer. Retrieved 2016-04-03.
  31. ↑ Kristen Philipkoski. "Mighty Mice Regrow Organs". Archive.wired.com. Retrieved 2016-04-03.
  32. ↑ "Ellen Heber-Katz: The MRL mouse - how it regenerates and how we might do the same on Vimeo". Vimeo.com. 2011-01-23. Retrieved 2016-04-03.

External links

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