PD Dr.med. Razvan Tudor Radulescu, M.D.

Since 1992 my main research focus has been to study the language of biologically relevant proteins or, in other terms, their structure-function relationships. To this end, I have founded the non-profit start-up Molecular Concepts Research (MCR).

I have been particularly interested in retinoblastoma protein (RB), insulin, insulin-like growth factors 1 and 2 (IGF-1 and IGF-2), insulin-like growth factor-binding proteins 3 and 5 (IGFBP-3 and IGFBP-5), insulin-degrading enzyme (IDE), the prion protein (PrP) and immunoglobulins/antibodies.

Among my discoveries are the physical interaction between insulin and RB, thus suggesting the existence of a previously unknown form of hormone/growth factor signalling I coined "nucleocrine pathway"; nuclear localization signals in IGFBP-3 and IGFBP-5; a putative tumor suppressor role for IDE, the latter of which I had already disclosed as part of a research collaboration in 1994, yet experimentally addressed only in the period 2004-2006 and, moreover, in 2009. Furthermore, I have unveiled a putative NADH binding site as well as a ribonucleoprotein (RNP) A1-like domain in PrP suggestive of (non-coding) nucleic acid binding and revealed zinc finger-like motifs in antibody constant regions, pointing to the possibility that these immunoglobulin domains may physically interact with DNA/RNA and thus directly affect their own production.

Last but not least, I have derived antineoplastic peptides from my analysis of the amino acid sequence of RB. These so-called MCR peptides have successfully been tested against various human tumor cells in the preclinical setting. Thus, MCR peptides hold great promise as candidate drugs for the clinical treatment of human cancer.

Selected publications

1. Radulescu, R.T. and Wendtner, C.M. 1992. Proposed interaction between insulin and retinoblastoma protein. J. Mol. Recognit. 5: 133-137.

2. Radulescu, R.T. and Wendtner, C.M. 1993. Hormone and growth factor subunits: a novel perception of cell growth regulation. J. Endocrinol. 139: 1-7.

3. Radulescu, R.T. 1994. Nuclear localization signal in insulin-like growth factor-binding protein type 3. Trends Biochem. Sci. 19: 278.

4. Radulescu, R.T., Bellitti, M.R., Ruvo, M., Cassani, G. and Fassina, G. 1995. Binding of the LXCXE insulin motif to a hexapeptide derived from retinoblastoma protein. Biochem. Biophys. Res. Commun. 206: 97-102.

5. Radulescu, R.T. 1995. From insulin, retinoblastoma protein and the insulin receptor to a new model on growth factor specificity: the nucleocrine pathway. J. Endocrinol. 146: 365-368.

6. Radulescu, R.T. 1998. Immune modulation by zinc: clues from immunoglobulin structure and function. Immunol. Today 19: 288.

7. Radulescu, R.T. and Jaques, G. 2000. Selective inhibition of human lung cancer cell growth by peptides derived from retinoblastoma protein. Biochem. Biophys. Res. Commun. 267: 71-76.

8. Radulescu, R.T., Doklea, E., Kehe, K. and Mückter, H. 2000. Nuclear colocalization and complex formation of insulin with retinoblastoma protein in HepG2 human hepatoma cells. J. Endocrinol. 166: R1-R4.

9. Radulescu, R.T. and Jaques, G. 2003. Potent in vivo antineoplastic activity of MCR peptides MCR-4 and MCR-14 against chemotherapy-resistant human small cell lung cancer. Drugs Exp. Clin. Res. 29: 69-74.

10. Radulescu, R.T. 2008. Going beyond the genetic view of cancer. Proc. Natl. Acad. Sci. U.S.A. 105: E12.

11. Radulescu, R.T. and Brenig, B. 2009. Infectious nucleic acids in prion disease: halfway there. Trends Biochem. Sci. 34: 4-5.

12. Radulescu, R.T., Poznic, M. and Pavelic K. 2009. Complex formation between metabolic enzymes in tumor cells: unfolding the MDR1-IDE paradigm. Mol. Cancer Ther. 8: 3171.