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Dan H. Schulze, PhD

Academic Title:

Professor

Primary Appointment:

Microbiology and Immunology

Secondary Appointment(s):

Otorhinolaryngology-Head & Neck Surgery

Additional Title:

Professor, Microbiology/Immunology and Otorhinolaryngology

Location:

BRB 3-031

Phone (Primary):

(410) 706-5180

Phone (Secondary):

(410) 706-4762

Fax:

(410) 706-2129

Education and Training

--Indiana University (Bloomington) BS, Zoology, 1969                      

--Miami University (Oxford) MS, Zoology (Genetics) 1972

--University of Texas (Austin), Ph.D., Zoology(Molecular Biology) 1977

--University of Minnesota, (St. Paul), Post-doctoral Study,

Department of Genetics and Molecular Biology, 1980   

 --Albert Einstein College of Medicine (Bronx), Post-doctoral

Study,Department of Immunology and Cell Biology, 1984

 

Biosketch

The immune system’s ability to identify possible threats is central in maintaining one’s basic health.  Dr. Schulze’s laboratory uses molecular biological approaches to study a several immunological topics.  Studies including determining the composition of the immune antibody repertoire, histocompatibility diversity generation, developing novel chimeric antigen receptors for T-cell based immunotherapy and recently utilizing Fc receptors to engineer novel biosensors are the major areas of research focus.   A non-immunological interest includes the study of ion transporters, specifically those involved with sodium/calcium regulation.  Studies in these research areas have resulted in multiple peer-reviewed publications.

 Dr. Schulze has trained seven students (Ph.D. and MS) and more than 20 postdoctoral fellows.  Recently he has organized and now is in charge of operating the Quality Systems Office for the School of Medicine which oversees Good Laboratory Practice (GLP) studies at the University.

Research/Clinical Keywords

Histocompatibility, sodium calcium exchange, Fc receptors, Natural Killer cells, biosensors

Highlighted Publications

 

Pease, L.R., D.H. Schulze, G. Pfaffenbach and S.G. Nathenson.  Spontaneous H-2 mutants provide evidence that a copy mechanism analogous to gene conversion generates polymorphism in the MHC. Proc. Natl. Acad. Sci. USA  80:242-246; 1983. (PMID: 6571997)

Schulze, D.H. and C.S. Lee. DNA sequence comparison among closely related Drosophila species in the Mulleri complex.  Genetics 113:287-303; 1986.  (PMID: 3721196)  

Schulze, D.H. and G. Kelsoe.  Genotypic analysis of B-cell colonies by in situ hybridization: Expression of three VH gene families in adult C57BL/6 and BALB/c mice. J. Exp. Med. 166:163-172; 1987.

Kofuji, P., W.J. Lederer and D.H. Schulze.  Mutually exclusive and cassette exons underlie alternately spliced isoforms of the Na+/Ca2+ exchanger.  J. Biol. Chem. 269:5145-5149, 1994 (PMID: 8106495). 

Jain AJ, Olsen HS, Vyzasatya R, Burch E, Sakoda Y, Merigeon EY, Block DS, Cai L, Lu C, Tan M, Tamada K, Schulze D, Strome SE: Fully Recombinant Murine StradomersTM Effectively Prevent Idiopathic Thrombocytopenic Purpura and Treat Arthritis in Mice. Arthritis Res. Ther 14:192, 2012  (PMID: 22906120).

 

Additional Publication Citations

Schulze D.H., L.R. Pease, Y. Obata, S.G. Nathenson, A.A. Reyes, S., Ikuta and R.B. Wallace.  Identification of the cloned gene for the murine transplantation antigen H-2Kb by hybridization with synthetic oligonucleotides.  Molec. Cell. Biol. 3:370-375; 1983. (PMID: 6855774)

Schulze, D.H., L.R. Pease, K. Yokoyama, S.S. Geier, G.M., Pfaffenbach, J. Geliebter, R.A. Zeff, B.P. Rosenblatt and S.G. Nathenson.  Diversity and polymorphism in the MHC appear to be generated by a copy mechanism. Transp. Proc. 15:2009-2012; 1983.  (PMID: 6673203).

Schulze, D.H., L.R. Pease, A.A. Reyes, L.A. Sarmiento, R.B. Wallace and S.G. Nathenson.  Comparison of the cloned H-2Kbml variant gene to the H-2Kb gene shows a cluster of seven nucleotide differences.  Proc. Natl. Acad. Sci. USA 80:2007-2011; 1983. 

Geliebter, J., R.A. Zeff, D.H. Schulze, L.R. Pease, E.H. Weiss, A.L. Mellor, R.A. Flavell and S.G. Nathenson.  Interaction between Kb and Q4 gene sequences generates the Kbm6 mutation.  Molec. Cell Biol.6:645-652; 1986. (PMID: 3023861)

Kelsoe, G., R. Miceli, J. Cerny and D.H. Schulze.  Mapping of antibody specificities of VH gene families.  Immunogenetics, 29:288-296; 1989.

Borghesi-Nicoletti, C. and D. H. Schulze. PCR amplification of genes flanked by short non-contiguous sequence motifs.  Anal. Biochem. 192:449-452; 1990. 

Miceli, R.M., Mancillas, P. and D.H. Schulze.  Analysis of the expressed heavy chain variable gene repertoire in aged mice.  Aging: Immunol. and Infectious Diseases 2:153-161; 1990

Schulze D.H. and E. Goidl.  Age-associated changes in antibody-forming cells (B cells).  Proc. Soc. Exp. Biol. and Med. 196:253-259; 1990.

 Schulze, D.H., P. Mancillas, A. Kaushik, C. Bona and G. Kelsoe.  Mitogen-induced VH and VL expression is similar in young adult and aged mice.  Aging: Immunology and Infection Diseases 3:127-134; 1992.

Kofuji, P., R.W. Hadley, R.S. Kieval, W.J. Lederer and D.H. Schulze.  Expression of the Na+/Ca2+ exchanger in diverse tissues:a study using the cloned human cardiac Na+/Ca2+ exchanger.  Am. J. Physiol. 263:C1241-C1249, 1992.  

Schulze, D.H., P. Kofuji, R. Hadley, M.S. Kirby, R. Kieval, A. Doering, E. Niggli and W.J. Lederer.  Sodium-calcium exchanger in heart muscle:  molecular biology.   Cellular function and its special role in excitation-contraction coupling.  Cardiovascular  Research 27:1726-1734, 1993. 

Kofuji, P., W.J. Lederer and D.H. Schulze. Na+/Ca2+ exchanger isoforms expressed in the heart and kidney.  Am. J. Physiol. 263:C1241-C1249, 1993

Ruknudin, A., C. Valdivia, P. Kofuji, W.J. Lederer and D.H. Schulze.  Na+/Ca2+ exchanger in Drosophila:  Cloning, expression and transport differences. Am J. Physiol.  273:C257-265,1997.

Ruknudin, A., S. He, W.J. Lederer and D. H. Schulze.  Functional differences between cardiac and renal isoforms of the Na+/Ca2+ exchanger, NCX1.  J. Physiology 529:599-610, 2000. 

He, S., A. Ruknudin, L.L. Bambrick, W.J. Lederer, and D.H. Schulze.  Isoform-specific regulation of the Na+/Ca2+ exchanger in rat astrocytes and neurons by PKA.  J. Neurosci.  18:4833-4841, 1998. (PMID: 9634549). 

Egger, M., A. Ruknudin, P. Lipp, P. Kofuji, W.J. Lederer, D.H. Schulze, E. Niggli.  Functional expression of the human cardiac Na+/Ca2+ exchanger in Sf9 cells:  rapid and specific Ni2+ transport.  Cell Calcium 25:9-17, 1999. 

Polumuri, S.K., A. Ruknudin and D.H. Schulze.  RNase H Treatment and its effects on PCR.  BioTechniques  July 2002.

Wei,  S.K., A. Ruknudin, S.U. Hanlon,  J.M. McCurley, D.H. Schulze, and M.C Haigney.  Protein Kinase A Hyperphosphorylation Increases Basal Current but Decreases {beta}-Adrenergic Responsiveness of the Sarcolemmal Na+-Ca2+ Exchanger in Failing Pig Myocytes.  Circ. Res.92(8):897-903 2003. 

Schulze D.H, Mughal M, Lederer WJ, Ruknudin AM.  Sodium/calcium exchanger (NCX1) macromolecular complex.  J. Biol. Chem.  278:28549-28555, 2003. 

Lin W, Voskens CJ, Zhang X, Schindler DG, Wood A, Burch E, Wei Y, Chen L, Tian G, Tamada K, Wang LX, Schulze DH, Mann D, Strome SE. Fc-dependent expression of CD137 on human NK cells: insights into “agonistic” effects of anti-CD137 monoclonal antibodies. Blood 112:699-707, 2008. (PMID:18519814).

 Taylor R.J., Chan S-L., Wood A., Voskens C.J., Wolf J.S., Wei, L., Chapoval, A., Schulze D.H., Cullen, K.,  Strome S.E. FcRIIIa polymorphisms and cetuximab induced cytotoxicity in squamous cell carcinoma of the head and neck. Cancer Immunol. Immunother 58:997-1006, 2009 (PMID: 18979096). 

Chan S-L, Voskens C.J., Lin, W., Schindler D.G., Azimzadeh A., Wang L-X., Taylor R. J., Strome S. E. and Schulze D. H.  Epitope mapping of a chimeric CD137 mAb: A necessary step for assessing the biologic relevance of non-human primate models. J. Mol. Recognition 22:242-249, 2009 (PMID: 19177494)

Zhang X, Voskens CL, Sallin M, Maniar A, MontesCL, Shang Y, Lin W, Li G, Burch E, Tan M, Hertzano R, Chapoval AI, Tamada, K Gastman BR, Schulze DH, Strome.  CD137 Promotes Proliferation and Survival of Human B Cells. J. Immunol. 184: 787-795, 2010 (PMID: 20008291). 

Giladi M, Bohbot H, Buki T, Schulze DH, Hiller, R. Khananshvilli D.  Dynamic Features of Allosteric Ca2+ Sensor in Tissue-Specific NCX Variants.  Cell Calcium 51:478-485, 2012.    (PMID:22571864). 

 Jain A, Poonia B, So EC, Vyzasatya R, Burch EE, Olsen HS, Mérigeon EY, Block DS, Zhang X, Schulze DH, Hanna NN, Twadell WS, Yfantis HG, Chan SL, Cai L, Strome SE.  Tumour antigen targeted monoclonal antibodies incorporating a novel multimerization domain significantlyh enhance antibody-dependent cellular cytoxicity against colon cancer.  Eur J Cancer. 49:3344-52, 2013 (PMID: 23871153).

So EC, Sallin MA, Zhang X, Chan SL, Sahni L, Schulze DH, Davila E, Strome SE, Jain A  A high throughput method for enhancement of natural killer cells and lymphocytes and assessment of in vitro cytotoxicity.  J Immunol Methods. 394:40-8, 2013 (PMID: 23680234). 

Research Interests

Having been trained as a molecular biologist various research fields were available.  After studying evolutionary relatedness for various Drosophila strains, I was introduced to Immunology and have continued almost completely in that field.  I studied diversity generation in histocompatability loci and in my first independent position I began studying the development of antibody repertoire and its diversity.  Using antibodies is a thread that has run through much of my research to date.

 

The goal of the proposed research is to study chimeric antigen receptor (CARs) in a subset of T cells, NKT cells.  The experiments described will study the function of this T cell subset both in vitro and using murine tumor models.  The anticipated benefit of this work is that this subset of T cells may prove more robust and change the current paradigm in cancer immunotherapy.  I am particularly interested in this study because recently my laboratory has worked on developing the use of chimeric antigen receptor constructs expressed in T cells not only to activate but to block interactions between tumor cells and the immune system that normally would result in inhibition of T cell function within the tumor environment.  Having been trained as a molecular biologist I originally studied mechanisms of generating antibody diversity.  Now in addition to the chimeric antigen receptor work, my laboratory has become interested in developing novel approaches to expand the ability to test for the presence of pathogens using a biosensor system.  I have engineered a construct that is composed of the antibody binding domain (the high affinity Fc receptor) linked to the transmembrane and signaling domains of Iga, the signaling/activation domain used to activate B cells.  This universal biosensor platform provides a rapid way to expand the testing capabilities by using commercially available monoclonal antibodies.  The development of this universal biosensor could have broad implications to any biosensor system that uses antibodies as their molecules for targeting and/or specificity.  As you can see my research has never been very far way from using antibodies in various research areas.  During >25 years in the field of molecular immunology and molecular biological approaches to study various aspects of the B cell immune repertoire,   I have also worked and published in the characterization of membrane transporter molecules that regulate Ca2+ in cells and studied alternatively spliced variants of immune co-stimulatory molecules.   I was also involved with basic experimental studies and intellectual property development for a Baltimore–based start-up, Gliknik with Dr. S. Strome.   

 

After moving to Maryland in 1989 in addition to studying Immunology questions he became interested in characterization of ion transporters.  My laboratory cloned both human and Drosophila sodium/calcium exchangers (NCXI) and were the first to identify and characterize alternative splicing of this transporter.

Awards and Affiliations

 

1968                       NSF Undergraduate Research Fellowship

1973-1977            NIH Genetics Training Grant

1980-1981            American Cancer Society Research Grant

2013                     Elected Member, Carolyn J.  Pass, MD’66 and Richard M. Susel MD’66, Academy of Educational Excellence, University of Maryland School of Medicine

Professional Activity

Previous positions

 --Teacher-Mathematics, Adams School, Hamilton, Ohio, 1969-1970

--Research Assistant, Miami University, Department of Zoology and Physiology, Oxford, Ohio, 1970-1972

--Teaching Assistant, University of Texas, Department of Zoology, Austin, Texas, 1972-1973

--Research Specialist, University of Minnesota, Department of Genetics and Cell Biology, St.  Paul, Minnesota,1978-1980

--Postdoctoral Fellow, Albert Einstein College of Medicine, Department of Microbiology and Immunology, Bronx, New York, 1980-1984

--Assistant Professor, University of Texas Medical Branch at Galveston, Department of Microbiology, Galveston, Texas, 1984-1989

--Assistant Professor, University of Maryland, School of Medicine, Department of Microbiology and Immunology, Baltimore, Maryland., 1989-1991

--Associate Professor (with tenure), University of Maryland, School of Medicine, Department of

Microbiology and Immunology, Baltimore, Maryland, 1991-2015.

--Associate Professor, University of Maryland, School of Medicine, Department of Otorhinolaryngology: Head and Neck Cancer, Baltimore, Maryland, 2006-2015