Brother DeSales Lawless: A Lifetime in the Sciences and Education

1. Brother DeSales Lawless:A Lifetime in the Sciences and Education MaryAnn Principato, Ph.D. Fordham University CLC ‘75

2. Brother DeSales Lawless • Born: 1920 Bardstown, Kentucky • Ordained : Xaverian Brother 1942 • Bachelor’s Degree: Catholic University • Ph.D. 1966 Science History GSAS/New York University • Ph.D. 1969 Biochemistry Basic Medical Sciences Program, GSAS/New York University • Fordham University CLC Faculty, Division of Mathematics and Natural Sciences 1969-2003 • Rockefeller University Researcher 1969(?)-2003.

3. A Student’s View… • A Southern drawl in Manhattan • “Oh for pity’s sake!” • “My, my such good apple pie!” • “See you around like a doughnut!” • Pied Piper of Students • Life at Rockefeller • Where is it in the textbook?

4. College Life 1971-1975

5. Heidelberger & Kabat Ochoa RNAp Benacerraf Ir Watson & Crick Niels Jerne Ab selection Maxine Singer, Norton Zinder, Paul Berg and others at Asilomar 1974 Consequences of Restriction enzymes Milstein hybridomas Baltimore Rev Trans Science Advancements in the mid 20th Century

6. The Years at Oak Ridge (1971-1975)… Studies with Gallium67 • The radioisotope Gallium67 was known to localize in a variety of human and rodent tumors. • At the time, the mechanism for attachment and entry into tumor tissue was not known. The subcellular distribution of the isotope is in liver microsomes. • Using the 5123C rat hepatoma, Brother Desales isolated and characterized the binding of the isotope to a 45,000 MW molecular weight glycoprotein localized in the microsomes. In D Lawless, David Brown, et.al., Isolation and Partial Characterization of a 67Ga binding Glycoprotein from Morris 5123C Rat Hepatoma.Cancer Research 38:4440. 1978

7. Gallium 67 continued • The isotope is used today for tumor imaging, yet the radiopharmaceutical remains a controversial tumor imaging agent. • While tumors are known to be highly vascularized, the isotope’s transport mechanism which facilitates entry into tissue has not been defined. • The isotope is known to be bound by transferrin as well as by the 45,000MW glycoprotein. However, the transport of the isotope is known to occur using both transferrin-dependent and transferrin –independent mechanisms. • The role of the 45000 MW glycoprotein has yet to be elucidated.

8. Dr. Charlotte Cunningham-Rundles The Years at Memorial Sloan-Kettering Cancer Center (1978-1985) • Brother DeSales began his training in Immunology with Dr Cunningham Rundles and Dr. Robert Good’s Division of Immunodeficiency and Allergy. • Combined biochemical expertise to solve immunochemical problems • Isolation of high molecular weight circulating antibody complexes. • Description of the presence of FcR on the surface of T lymphocytes C. Cunningham-Rundles, D. Lawless, S. Gupta, C. Galanos, R.A. Good. Isolation and partial chemical characterization of the IgG Fc receptor of human T lymphocytes and production of an antiserum. PNAS 77:3645.1980.

9. The Years with the Naval Medical Research Institute,Bethesda,MD.(1986-1987) • Coupling antibodies of defined specificity to beads • Isolation of human precursor and stem cells • Expansion of stem cells

10. Colon Cancer Research at Oak Ridge (1987-1988) • Method development for the detection of circulating colon cancer cells in an animal model • Development of an ELISA assay for the detection of host circulating antibodies directed against the surface adenocarcinoma glycoprotein • B.DeSales Lawless, Y. Lee, J. Crook, N. Clapp. ELISA assay for Colon Cancer. J Clin Lab. Analysis. 2:35. 1988. • B.DeSales Lawless, Y. Lee, J. Crook, N. Clapp. Colon Cancer Cellsin Peripheral Blood of Cancerous Tamarins. Clin Immunol.Immuopath.48:338.1988.

11. The Years with NASA 1990-1998

12. The Effects of Space flight upon Cellular Immune Function • Increased susceptibility to infection (Apollo missions). • Decreased responsiveness to recall antigen skin tests. • Peripheral blood lymphocytes derived from returning astronauts are refractory to mitogenic stimulation. • Astronauts exhibit temporary changes in CD4/CD8 T cell ratios. • Reduced production of IL-2 cytokine and IL2 receptor. • Hypothesis: Lack of immune response occurs at the cellular level.

13. STS 56 CMIX 2 Mission: The Immune Function of T cells • Method: Stimulation of purified murine splenic T cells through direct engagement of the T cell receptor with the SEB superantigen or via the TCR-associated CD3 molecule using anti-CD3+1L2. • Result: In both instances, the murine T cell population transitioned into DNA synthesis (S phase) and mitotic division (G2+M), indicative of cellular proliferation. • Assay: Cell cycle analysis by flow cytometry Principato, M.A., B.D. Lawless, and M.L. Lewis. Superantigen-mediated T cell receptor stimulation in zero gravity. ASGSB Bulletin Vol. 7:, (1993).

14. STS-56 Night Launch…“T minus 11 seconds”

15. CMIX 4 Experiments on STS 69 M.L Lewis, M.A Principato, B D. Lawless, D.R. Morrison, W.C. Kapp, S.L. Strobl and AC. Ochoa EFFECTS OF MICROGRAVITY ON LEUKOCYTE GROWTH CONTROL AND FUNCTION. In Molecular Biology of the Cell 4:450 (1993) Department of Biology, Univ. of Alabama, Huntsville, AL 35899, Immunology Branch, Food and Drug Administration. Laurel, MD 20708, Dept of Cellular Immunology, Rockefeller Univ., NY, NY 10021 NASA Johnson Space Center, Houston, TX. 77058 and Program Resources Inc., DynCorp, Frederick MD 21702.

16. Spaceflight -induced Apoptosis and changes in the Cytoskeleton • Jurkat cells exhibited marked changes in cytoskeletal organization 4 hours into spaceflight. • Increased secretion of FAS • DNA replication occurred in flight. However , there was no progression through G2M phase as measured by flow cytometry. Taken from M. Lewis, J. Reynolds, L. Cubano, J. Hatton, B. DeSales Lawless, E. Piepmeir. Spaceflight alters microtubules and increases apoptosis in human lymphocytes (Jurkat). FASEB .J. 12:1007. 1998.

17. Spaceflight-induced alteration of cellular structure and physiology • Bone loss in spaceflight • Altered Nuclear morphology • Altered actin and microtubule organization Dr. Millie Fulford -Hughes

18. Human Physiology at NASA’s Ames Research Center • Problem: Spaceflight deconditioning includes reduced body water and blood volume (hypovolemia), as well as decreased aerobic capability and immune function. • This research examined the effect of fluid replacement on exercise-induced hypovolemia and immune function In J.E. Greenleaf, C.G. R. Jackson, and D. Lawless.CD4/CD8 Lymphocyte Ratio: effects of rehydration before exercise in dehydrated men. Medicine and Science in Sports and Exercise 27:194. 1995 Lawless, D., C.G. Jackson, J.E. Greenleaf. Exercise and Human Immunodeficiency Virus.19:235. 1995

19. Time at the FDA..Summer of 1996 • Hijinks and hilarity with Kenny and Amy • Glycoconjugate mapping

20. Rockefeller UniversityAdditional activities • Protein sequencing of phage lambda. P. Model & N. Zinder. Laboratory of Genetics • Isolation and characterization of Dendritic cells R. Steinman Laboratory of Cellular Physiology and Immunology

21. The Last Proposal: The Immunofunctionality of CD8+ T Cells in AIDS • For his last research proposal, Brother attracted the attention of Dr. Anthony Fauci of the National Institutes of Health. He proposed to examine and exploit the immunofunctionality of CD8+ T cells for the treatment of AIDS. • However, advancing age and infirmity, coupled with a younger and more aggressive scientific culture, prevented Brother’s last success. • A publication from the AIDS Research Center of Harvard University supports Brother’s last premise: Immunodominance of HIV-1-specific CD8+ T cell responses in acute HIV-1 infection: at the crossroads of viral and host genetics. Mathias Lichterfeld, et. al. in Trends in Immunology 26(3):166-171. 2005

22. Retirement in Kentucky 2003-2008

23. Brother DeSales:Professor, Mentor, Colleague, and Friend Brother DeSales passed away on Feb. 29, 2008 in his hometown of Louisville, Ky.

24. My cat Katey (Katrina) was born on Feb. 29, 2008, and continues Brother’s inquisitive and comedic spirit.