Courtyard of the Medical Library at the College of Medicine, University of Illinois, Chicago. The statue is in remembrance of Aesculapius, the mythological god of healing, and was donated by Alpha Omega Alpha, the Honor Medical Society. The library is a beacon of inspiration for all physicians, and we are eternally grateful for its light. - John H. Frenster, M.D.

Artist: Robert W. Addison, Chicago.

John H. Frenster M.D. FACP
RNA Research
Physicians' Educational Series
247 Stockbridge Avenue
Atherton, CA 94027-5446, USA
Phone:  +1 650 367 6483
Fax:  +1 650 364 1773
e-mail:  frensterjh@aol.com

Born in Chicago, Illinois USA, October 14, 1928.
B.S. in Chemistry, (Highest Honors), University of Illinois, Champaign-Urbana, 1950.
M.D. (Honors), College of Medicine, University of Illinois, Chicago, 1954.
Medical Internship: Cook County Hospital, Chicago, 1954-1955.
Medical Residency and Hematology Fellowship, University of Illinois Research Hospital, Chicago, 1955-1958.
ACS Post-Doctoral Fellowship, Dr. Alfred E. Mirsky, Rockefeller University, New York, 1958-1960.
Captain, US Army Medical Corps, Walter Reed Army Medical Center, Washington, DC, 1960-1962.
Assistant Professor, Cell Biology, Rockefeller University, New York, 1962-1965.
Assistant Professor of Medicine (Medical Oncology), Stanford University, Stanford, CA, 1966-1973.
Clin. Associate Professor of Medicine (Medical Oncology), Stanford University, Stanford, CA, 1973-1994.
President, Physicians' Educational Series, Atherton, California, 1994-Present.
Editor, The Euchromatin Network, http://www.euchromatin.net/ 1998-Present.

USPHS Research Career Development Award, National Cancer Institute, 1962-1967.
Research Scholar, Leukemia Society, 1967-1972.
Fellow, American College of Physicians, 1971-Present.
Kaiser Award for Excellence in Clinical Teaching, Stanford University Medical School, 1972, 1973. 

American Association for Cancer Research, 1961-Present
American Society for Cell Biology, 1962-Present
American College of Physicians, 1966-Present
Biophysical Society, 1970-Present
American Society of Clinical Oncology. 1970-Present
Western Society for Clinical Investigation, 1972-Present
RNA Society, 2000-Present

1. Frenster JH, Best WR, Winzler RJ, METABOLISM OF HUMAN LEUKOCYTES IN VITRO. V. INHIBITION BY HUMAN SERUM OF FORMATE AND GLYCINE INCORPORATION, Proc Soc Exp Biol Med 98, 887-890 (1958).

2. Frenster JH, Allfrey VG, Mirsky AE, METABOLISM AND MORPHOLOGY OF
RIBONUCLEOPROTEIN PARTICLES FROM THE CELL NUCLEUS OF LYMPHOCYTES, Proc Natl Acad Sci USA 46, 432-444 (1960).

3. Frenster JH, LIMITS TO FUNCTIONAL HYPERTROPHY IN HIGH-OUTPUT FAILURE, Ann Int Med 53, 647-655 (1960).

4. Allfrey VG, Hopkins JW, Frenster JH, Mirsky AE, REACTIONS GOVERNING THE INCORPORATION OF AMINO ACIDS INTO THE PROTEINS OF THE ISOLATED CELL NUCLEUS, Ann NY Acad Sci 88, 722-740 (1960).

5. Frenster JH, INTERACTION OF LOAD, CAPACITY AND RESISTANCE IN BODY PROCESSES, Persp Biol Med 4, 152-158 (1961).

6. Frenster JH, Allfrey VG, Mirsky AE, IN-VITRO INCORPORATION OF AMINO ACIDS INTO THE PROTEINS OF ISOLATED NUCLEAR RIBOSOMES, Biochim Biophys Acta 47, 130-136 (1961).

7. Frenster JH, THE MAGNITUDE OF DISEASE AS MEASURED BY TOLERANCE TESTS, J Theo Biol 2, 159-164 (1962).

8. Frenster JH, LOAD-TOLERANCE AS A QUANTITATIVE ESTIMATE OF HEALTH, Ann Int Med 57, 788-794 (1962).

9. Frenster JH, CONSTRAINTS ON ISOLATION OF MAMMALIAN CHROMOSOMES, Exp Cell Res 9, 235-238 (1963).

10. Frenster JH, Allfrey VG, Mirsky AE, REPRESSED AND ACTIVE CHROMATIN ISOLATED FROM INTERPHASE LYMPHOCYTES, Proc Natl Acad Sci USA 50, 1026-1032 (1963).

11. Frenster JH, HUMAN THROUGHPUT SYSTEMS, Proc Ann Conf Engin Biol Med 5, 164-165 (1963).

12. Littau VC, Allfrey VG, Frenster JH, Mirsky AE, ACTIVE AND INACTIVE REGIONS OF NUCLEAR CHROMATIN AS REVEALED BY ELECTRON MICROSCOPE AUTORADIOGRAPHY, Proc Natl Acad Sci USA 52, 93-100 (1964).

13. Frenster JH, ULTRASTRUCTURAL CONTINUITY BETWEEN ACTIVE AND REPRESSED CHROMATIN, Nature 205, 1341-1342 (1965).

14. Frenster JH, NUCLEAR POLYANIONS AS DE-REPRESSORS OF SYNTHESIS OF RIBONUCLEIC ACID, Nature 206, 680-683 (1965).

15. Frenster JH, A MODEL OF SPECIFIC DE-REPRESSION WITHIN INTERPHASE CHROMATIN, Nature 206, 1269-1270 (1965).

16. Frenster JH, ANALYSIS OF QUEUEING AND RENEWAL WITHIN HUMAN SYSTEMS, Nature 207, 1139-1140 (1965).

17. Frenster JH, LOCALIZED STRAND SEPARATIONS WITHIN DEOXYRIBONUCLEIC ACID DURING SELECTIVE TRANSCRIPTION, Nature 208, 894-896 (1965).

18. Frenster JH, CORRELATION OF THE BINDING TO DNA LOOPS OR TO DNA HELICES WITH THE EFFECT ON RNA SYNTHESIS, Nature 208, 1093-1094 (1965).

19. Frenster JH, MECHANISMS OF REPRESSION AND DE-REPRESSION WITHIN INTERPHASE CHROMATIN, in "The Chromosomes: Structural and Functional Aspects", 78-101, edit. by Dawe DJ, Yerganian G, (Williams and Wilkens, Inc. Baltimore/1965), and also published in: In-Vitro, vol. 1, pp. 78-101, (1965).

20. Rose HG, Frenster JH, COMPOSITION AND METABOLISM OF LIPIDS WITHIN REPRESSED AND ACTIVE CHROMATIN OF INTERPHASE LYMPHOCYTES, Biochim Biophys Acta 106, 577-591 (1965).

21. Frenster JH, CONTROL OF DNA STRAND SEPARATIONS DURING SELECTIVE TRANSCRIPTION AND ASYNCHRONOUS REPLICATION, in "The Cell Nucleus, Metabolism and Radiosensitivity", 27-46, edit. by Klouwen HM, (Taylor-Francis Ltd. London/1966).

22. Frenster JH, Rogoway WM, IN-VITRO ACTIVATION AND RE-INFUSION OF AUTOLOGOUS HUMAN LYMPHOCYTES, Lancet 2, 979-980 (1968).

23. Frenster JH, BIOCHEMISTRY AND MOLECULAR BIOPHYSICS OF HETEROCHROMATIN AND EUCHROMATIN, in "Handbook of Molecular Cytology", 251-287, edit. by Lima-de-faria A, (John Wiley and Sons, Inc. New York/1969).

24. Stanley DA, Frenster JH, Rigas DA, LOCALIZATION OF H3-PHYTOHEMAGGLUTININ WITHIN HUMAN LYMPHOCYTES AND MONOCYTES, in "Fourth Annual Leukocyte Culture Conference, 1969", 1-11, edit. by McIntyre OR, (Appleton-Century-Crofts, Inc. New York/1971).

25. Keshgegian AA, Meisner LF, Frenster JH, THYMIDINE REVERSAL OF RIBOTHYMIDINE INHIBITION OF LYMPHOCYTE MITOSIS, in "Fourth Annual Leukocyte Culture Conference, 1969", 361-366, edit. by McIntyre OR, Appleton-Century-Crofts, Inc. New York/1971).

26. Frenster JH, Rogoway WM, IMMUNOTHERAPY OF HUMAN NEOPLASMS WITH AUTOLOGOUS LYMPHOCYTES ACTIVATED IN-VITRO, in "Fifth Annual Leukocyte Culture Conference, 1970", 359-373, edit. by Harris JE, (Academic Press, Inc. New York/1970).

27. Frenster JH, ELECTRON MICROSCOPIC LOCALIZATION OF ACRIDINE ORANGE BINDING TO DNA WITHIN HUMAN LEUKEMIC BONE MARROW CELLS, Cancer Res 31, 1128-1133 (1971).

28. Allen BL, Frenster JH, LOW-DOSE COMBINATION CHEMOTHERAPY OF DISSEMINATED HUMAN NEOPLASMS, Lancet 2, 1324 (1971).

29. Frenster JH, ULTRASTRUCTURAL MOLECULAR PROBES OF CHROMATIN CONFORMATION STATES WITHIN LIVING HUMAN LYMPHOCYTES, Nature 236, 175-176 (1972).

30. Frenster JH, ULTRASTRUCTURAL BINDING SITES CORRELATE WITH EFFECTS OF NUCLEAR LIGANDS ON RNA SYNTHESIS WITHIN HUMAN LEUKOCYTES, in "International Symposium on Structure and Functions of the Cell Nucleus", 159-168, edit. by Zbarsky IB, (Inst. Develop. Biol. Moscow: 1972).

31. Herstein PR, Frenster JH, MATED MODELS OF GENE REGULATION BY EUKARYOTES, in "Embryonic and Fetal Antigens in Cancer. Vol. 2", 3-5, edit. by Anderson NG, Coggin JH, (National Technical Information Service, US Dept of Commerce, Springfield VA/1972).

32. Frenster JH, Herstein PR, GENE DE-REPRESSION, New Eng J Med 288, 1224-1229 (1973).

33. Archibald RB, Frenster JH, QUANTITATIVE ULTRASTRUCTURAL ANALYSIS OF
    LYMPHOCYTE-REED STERNBERG CELL INTERACTIONS IN HODGKIN'S DISEASE, Monogr Natl Cancer Inst 36, 239-245 (1973).

34. Frenster JH, Herstein PR, RNA IN GENE DE-REPRESSION, in "The Role of RNA in Reproduction and Development", 330-338, edit. by Niu MC, Segal EJ, (North-Holland Publ Co., Amsterdam, London/1974).

35. Frenster JH, ULTRASTRUCTURE AND FUNCTION OF HETEROCHROMATIN AND
EUCHROMATIN, in "The Cell Nucleus, Vol 1", 565-580, edit. by Busch H, (Academic Press, Inc. New York: 1974).

36. Frenster JH, Nakatsu SL, Masek MA, ULTRASTRUCTURAL PROBES OF DNA TEMPLATES WITHIN HUMAN BONE MARROW AND LYMPH NODE CELLS, Adv Cell Molec Biol 3, 1-20 (1974).

37. Nakatsu SL, Masek MA, Landrum S, Frenster JH, ACTIVITY OF DNA TEMPLATES DURING CELL DIVISION AND CELL DIFFERENTIATION, Nature 248, 334-335 (1974).

38. Frenster JH, ULTRASTRUCTURAL PROBES OF CHROMATIN DURING CELL DIVISION AND CELL DIFFERENTIATION, in "Proc 9th Annual Meeting, Vol 33", 419-428, (Fed. Europ. Biochem. Socs., Amsterdam: 1975).

39. Frenster JH, GENE REGULATION: SELECTIVE CONTROL OF DNA HELIX OPENINGS, in "The Role of Nucleic Acid Addition Reactions", 53-66, edit. by Smith KC, (Plenum Publ Co., New York: 1976).

40. Frenster JH, SELECTIVE CONTROL OF DNA HELIX OPENINGS DURING GENE REGULATION, Cancer Res 36, 3394-3398 (1976).

41. Frenster JH, Landrum S, Masek MA, Nakatsu SL, Wilson LS, CONTROL OF DNA HELIX OPENINGS DURING IN-VIVO NORMAL AND NEOPLASTIC CELL MATURATION, in "Onco-Developmental Gene Expression", 107-114, edit. by Fishman WH, Sell S, (Academic Press, Inc. New York: 1976).

42. Frenster JH, PHYTOHEMAGGLUTININ-ACTIVATED AUTOCHTHONOUS LYMPHOCYTES FOR SYSTEMIC IMMUNOTHERAPY OF HUMAN NEOPLASMS, Ann NY Acad Sci 277, 45-51 (1976).

43. Frenster JH, Papalian MM, Masek MA, Frenster JA, ELECTRON MICROSCOPIC ANALYSIS OF LYMPH NODE CELLULAR ACTIVITY IN HODGKIN'S DISEASE, J Natl Cancer Inst 63, 331-335 (1979).

44. Frenster JH, SELECTIVE GENE DE-REPRESSION BY DE-REPRESSOR RNA, in "Eukaryotic Gene Regulation, Vol 1, Chap 4", 131-143, edit. by Kolodny GM, (CRC Press, Inc. BocaRaton,FL: 1980).

45. Frenster JH, ELECTRON MICROSCOPIC ANALYSIS OF ACTIVE AND REPRESSED CHROMATIN WITHIN NORMAL AND NEOPLASTIC HUMAN CELLS, in "Proc 38th Annual Meeting Electron Microscopy Society of America", 542-543, edit. by Bailey GW, (Claitor's Publ. Div. Baton Rouge, LA: 1980).

46. Frenster JH, ELECTRON MICROSCOPIC ANALYSIS OF ASYMMETRY WITHIN THE CELL NUCLEUS OF DNA HELIX OPENINGS DURING CELL ACTIVATION AND CELL DIFFERENTIATION, in "Proc 38th Annual Meeting Electron Microscopy Society of America", 544-545, edit. by Bailey GW, (Claitor's Publ. Div. Baton Rouge, LA: 1980).

47. Frenster JH, SINGLE-CELL ANALYSIS OF DNASE I-SENSITIVE SITES DURING NEOPLASTIC CELL DIFFERENTIATION WITHIN HODGKIN'S DISEASE LYMPH NODES, in "Leukemia Reviews International, Vol 1", 22-23, edit. by Rich MA, (Marcel Dekker, Inc. New York: 1983).

48. Frenster JH, EXPERT SYSTEMS AND OPEN SYSTEMS IN MEDICAL ARTIFICIAL INTELLIGENCE, Proc 1989 Cong Med Inform, AAMSI 7, 118-120 (1989).

49. Frenster JH, MATRIX COGNITION IN MEDICAL DECISION-MAKING, Proc 1989 Cong Med Inform, AAMSI 7, 131-134 (1989).

50. Frenster JH, SINGLE-CELL ANALYSIS OF DNASE I-SENSITIVE SITES DURING NEOPLASTIC AND NORMAL CELL DIFFERENTIATION WITHIN HUMAN BONE MARROW, Ann NY Acad Sci 567, 334-336 (1989).

51. Frenster JH, MATRIX COGNITION IN MEDICAL ARTIFICIAL INTELLIGENCE, Proc 11th Ann Int Conf IEEE Eng Med Biol Soc 11, 1821-1822 (1989).

52. Frenster JH, EIGENVECTOR FUNCTIONS IN MATRIX COGNITION DURING MEDICAL DIAGNOSIS, Proc 12th Ann Int Conf IEEE Eng Med Biol Soc 12, 1256-1257 (1990).

53. Frenster JH, NEURAL NETWORKS FOR PATTERN RECOGNITION IN MEDICAL DIAGNOSIS, Proc 12th Ann Int Conf IEEE Eng Med Biol Soc 12, 1423-1424 (1990).

54. Frenster JH, NUCLEAR RNA SPECIES ACTIVATE TRANSCRIPTION WITHIN CHROMATIN, FASEB J. 13: A1506 (April, 1999).

55. Frenster JH, ONCOGENES AS MOLECULAR TARGETS WITHIN ACTIVE CHROMATIN, Clin. Cancer Res. 5: suppl. 1, 3855a (November, 1999).

56. Hovsepian JA, and Frenster JH, RNA-INDUCED MELTING OF DNA DURING SELECTIVE GENE TRANSCRIPTION, Molec. Biol. Cell 13: suppl. 239a (2002).

57. Frenster JH, UNI-POLAR CLUSTERING OF LYMPHOCYTE DNA TEMPLATES TOWARD NEOPLASTIC TARGET CELLS WITHIN HODGKIN'S DISEASE LYMPH NODES, Proc. Am. Assoc. Cancer Res. 43: 1134 (2002).

58. Frenster JH, YEAST RNA RE-PROGRAMMING OF ALREADY-ACTIVE MAMMALIAN
CHROMATIN, RNA2002: 592 (The RNA Society, Bethesda, MD/2002).

59. Frenster JH, and Hovsepian JA, OVERSHOOT IN LATE TELOPHASE FOR RNA
RE-PROGRAMMING OF MITOTIC CHROMATIN, RNA2003: 211, (The RNA Society, Bethesda,
MD/2003).

60. Hovsepian JA, and Frenster JH,  EUCHROMATIN AS AN EXTENSILE  FORCE  WITHIN
 MAMMALIAN  CELL  NUCLEI. Molec. Biol. Cell, vol. 14, supp. 93a (Nov., 2003).

61. Hovsepian JA, and Frenster JH,  BIOASSAYS  OF  ISOLATED NUCLEAR RNA SPECIES  AS ACTIVATORS of DNA TRANSCRIPTION,  Molec. Biol. Cell, vol. 14, supp. 242a (Nov., 2003).

62. Frenster JH, and Hovsepian JA, ACTIVATOR  RNA  EXCHANGE  DURING  INTERPHASE CHROMATIN  REPROGRAMMING, RNA2004: 305 (The RNA Society, Bethesda, MD, 2004).

63. Frenster JH, and  Hovsepian JA, ,  ULTRASTRUCTURE  OF  CLOSED  LOOPS  WITHIN
EUCHROMATIN  OF  ISOLATED  LYMPHOCYTE  NUCLEI,  Molecular Biology of the Cell, vol. 15, suppl. p. 450 (November, 2004).

64. Hovsepian JA, and Frenster JH, "SENSE  AND ANTISENSE DURING RNA INITIATION OF THE DNA TRANSCRIPTION  BUBBLE", RNA2005: 279 (The RNA Society, Bethesda, MD 2005).

65. Frenster JH, and Hovsepian JA, "Ultrastructure of Euchromatin Contact Points between the Closed Loops of Adjacent Interphase Chromosomes", Molecular Biology of the Cell, vol.16, suppl. #1280 (November, 2005).

66. Frenster JH, and Hovsepian JA, "Kissing Chromosomes and Paired Sense-Antisense RNA Synthesis",
Cold Spring Harbor Symposium on Quantitative Biology, vol. 71, p. 62 (May 31-June 5, 2006).

67. Hovsepian JA, and Frenster JH,  "Chromosome-Chromosome Contact Points and Paired Sense-Antisense RNA Synthesis", RNA 2006, p. 237, June 20-25, 2006, The RNA Society, Bethesda, MD.

68. Frenster JH, and Hovsepian JA, "DNase-I Ultrastructural Probe Sites and Kissing Chromosomes", Molecular Biology of the Cell, vol.17, suppl. #1853 (November, 2006).

69. Frenster JH, and Hovsepian JA, "DNA-DNA Tetraplex Model of Paired Sense-Antisense RNA Synthesis",
RNA2007, p. 186, May 29-June 3, 2007, The RNA Society, Bethesda, MD.

70. Frenster JH, and Hovsepian JA,  “Models of Embryonic Gene-Induced Initiation and Reversion of Adult Neoplasms”. Presented at the AACR-NCI-EORTC International Conference: “Molecular Targets and Cancer Therapeutics: Discovery, Biology, and Clinical Applications”, p. 258-9, October 25, 2007, Moscone West Conference Center, San Francisco, California.

Dr. John Frenster is a pioneer in the fields of the cell nucleus, and of the role played by chromatin structure in the regulation of mammalian gene activity. His early studies are original for the identification, isolation, and analysis of repressed heterochromatin and active euchromatin, and in the utilization of these isolated chromatin fractions as bioassays of nuclear ligands which have activity as gene regulators. His 1963 paper (reference 10, above) was the first method for the separation of the active from the repressed portions of the mammalian genome, and a series of papers in 1965 provided the original data concerning euchromatin ultrastructure (ref. 13), euchromatin polyanions (ref. 14), and the ability of these polyanions to activate repressed heterochromatin in the bio-assay system. His discovery that small nuclear RNA species are the most active molecular species for effecting gene activation (ref. 15) was the beginning of the RNA model of gene regulation. His most recent studies are providing more molecular details of the vital role played by small nuclear activator RNA species in re-programming the genome either during interphase (ref. 58) or during the telophase stage of cell mitosis (ref. 59), and of the ultrastructure of closed chromatin loops within mammalian cell nuclei (ref. 63).  Such basic studies now permit a role for activator RNA in the re-programming of differentiated cells (ref. 62), even cancer cells (Hovsepian JA, and Frenster JH, "Reprogramming as an Approach to Neoplasms", 2004; Eder M, and Scherr M, "MicroRNA and Lung Cancer" , 2005).

In addition, his early studies were also the first to reveal the conformation change in the DNA helix during gene transcription (ref. 17), with a demonstration of biophysical separation of DNA strands, and a close parallel effect of ligands preferring to bind to single-stranded DNA with an effect of increasing gene transcription (ref. 18). These early studies on DNA conformation states during gene activation led him to discover the effect of DNase I on active chromatin (ref. 27), and to develop a high-resolution electron-microscopic probe technique for detecting and measuring active DNA sites with intact cells during cell division and cell differentiation (ref. 37). He then applied these ultrastructural probe techniques to the analysis of intact human cancer cells obtained directly from patients (ref. 27, 43), especially in Hodgkin’s lymphoma (ref. 43), with the discovery of an abortive form of cell differentiation in the neoplastic Reed-Sternberg cells (ref. 50), and an increased activation of DNA sites within T-lymphocytes apposed to the neoplastic cells. These studies have currently revealed a uni-polar clustering of active DNA sites into that portion of the T-lymphocyte nucleus closest to the target neoplastic cells, consistent with an immune attack by the T-lymphocytes against the target B neoplastic cells (ref. 57).  These basic studies also now permit new forms of immunotherapy for patients with Hodgkin’s lymphoma (Carella AM, "Stem Cell Transplantation for Hodgkin's Disease: A Review of the Literature", Clinical Lymphoma, vol. 2, no. 4, pp. 212-221 (March, 2002) ; Bollard CM, Aguilar L, Straathof KC, Gahn B, Huls MH, Rousseau A, Sixbey J, Gresik MV, Carrum G, Hudson M, Dilloo D, Gee A, Brenner MK, Rooney CM, and Heslop HE, "Cytotoxic T Lymphocyte Therapy for Epstein-Barr Virus⁺ Hodgkin's Disease", J. Exp. Med. 2004 200: 1623-1633.)

Most recently he has developed an integrated series of molecular models of embryonic gene re-expression within adult neoplasms:

Frenster JH, and Hovsepian JA,  “Models of Embryonic Gene-Induced Initiation and Reversion of Adult Neoplasms”. Presented at the AACR-NCI-EORTC International Conference: “Molecular Targets and Cancer Therapeutics: Discovery, Biology, and Clinical Applications”, p. 258-9, October 25, 2007, Moscone West Conference Center, San Francisco, California.

Please also see his Euchromatin Network archival web site at:
http://www.euchromatin.net/

Links to Euchromatin Activator RNA Reviews:
Links to Euchromatin Activator RNA Research:
Links to Ultrastructural Probes of DNase I-Sensitive Sites:
Links to RNA as a Therapeutic Agent:
Links to Hodgkin Lymphoma Immuno-Pathology:
Links to Activated T-Lymphocyte Immunotherapy:
Links to Medical Systems Biology:
Links to Selective Gene Transcription:
Links to RNA-Induced Epigenetics:
Links to RNA-Induced Embryogenesis:
Links to RNA and Biological Causality:
Links to Reprogramming and Neoplasia:

A Brief History of Activator RNA:

"Ultrastructural Probes of Active DNA Sites, and the RNA Activators of DNA". (PowerPoint Presentation).

e-mail:  frensterjh@aol.com
Phone:   +1 650 367 6483
Fax:   +1 650 364 1773