ד"ר אלימלך רוכלין

2002 Ph. D. in Organic Chemistry Hebrew University (HU), Jerusalem, Israel
Advisor: Prof. Zvi Rappoport
Thesis: "Stable Simple Enols. Structure, Thermodynamics and Stereochemistry".

1980 M. Sc. in Organic Chemistry Leningrad (St. Petersburg) State University, Russia
Advisor: Dr. V. Ketlinsky
Thesis “Red-Ox properties of thiocyanine organic dyes”

10/2013 – present Lecturer Dept. Bioinformatics, JCT
2018 – present Lecturer and Research Associate Dept. Biochemistry Food Scince and Nutrition, Faculty of Agriculture, Food and Environment, HU
2002 – 2013 External Lecturer Biochemistry, JCT
6/2004 – 8/2005 Research Fellow Dept. Organic Chemistry HU and Dept. Bone Marrow Transplantation Hadassah Medical Center
1989 – 1994 Doctorate Fellow, Assistant Dept. Organic Chemistry, HU

8/2005 – 12/2012 Head of Chemistry NasVax Ltd, (A biotech start-up with proprietary
immunotherapy technologies) Ness-Zionna, Israel
Responsible for developing candidate lipid-based delivery platforms. Supervised the development, implementation and execution of synthetic strategy, formulation, analytical methods and process development for sphingolipid-polyamine conjugates for vaccine delivery and adjuvant use. Responsible for analytical methods, formulation development and stability studies of therapeutic monoclonal antibody
12/1994 - 3/2004 Chief Chemist Lipiderm Ltd. (A start-up with proprietary technology for production of synthetic sphingolipids for research and pharmaceutical use)
Responsible for development, validation and deployment of processes for total synthesis of sphingolipids for research and pharmaceutical use. Supervised two Scientists and four technicians.
10/1996-3/2004 Head of Custom Organic Synthesis Lab Biolab Ltd.
Responsible for the development and production of a broad variety of small organic molecules
for a large number of customers in Israel and abroad including Teva, Genzyme, Chemagis, ACROS, Avanti, French Committee for Atomic Energy (CEA), etc.

1992  Yashinsky Prize in Natural Sciences-Hebrew University

1. Summary of Past Research and Development Activities. My past R&D activities concerned different areas of physical organic and synthetic organic chemistry as well as technologies for drug/vaccine delivery, stabilization of large biomolecules and pharmaceutical formulations of monoclonal antibodies.
   • Physical organic chemistry research was carried out in HU and dealt with sterically crowded simple enols and factors responsible for their unusual thermodynamic stability. This group of molecules can be isolated and are stable relative to their keto-tautomers, as opposed to other representatives of this vast class of molecules, which regularly appear as reactive intermediates but cannot be isolated. The research revealed that a delicate balance of conjugation and steric effects is responsible for their thermodynamic stability and solvent stabilization can further reinforce these effects. Investigation of internal rotations in these molecules, which have structure and dynamic behavior resembling molecular propellers, comprised a related research topic. Correlated rotations of aryl rings in these molecules was studied by means of dynamic NMR and appeared to have relatively high activation barriers which enabled to separate and isolate enantiomeric right- and left-handed propellers and to study the enantiomerization process by means of chiral HPLC. These studies were published in top-level chemical journals.
   • Synthetic organic chemistry developments were carried out as part of my duties as a Chief Chemist in Lipiderm ltd. The primary goal was to develop economically effective industrial process for manufacture of synthetic enantiomerically pure D-erythro-sphingosine and other related sphingolipids. The need for such a process arose on one hand from the increased interest to this compounds in pharma, cosmetic and research areas due to their key functions in many apoptotic, senescence and survival and growth processes. And on the other hand, traditional sources of these compounds, i.e., organic tissues and especially bovine brains were found to cause safety problems (e.g. CJD or mad cow disease and others). The process was successfully developed and patented and it is now in use by Biolab ltd. in Jerusalem for manufacture of stereochemically pure human ceramides and other sphingolipids. Another important development was CCS – new cationic sphingolipid, which first appeared to be a good DNA carrier for transfections and then found as an efficient carrier for protein vaccines, which furthermore, amplifies manifold vaccine immunogenicity. CCS and related class of compounds were patented and the rights for its use as a vaccines adjuvant were acquired by NasVax Ltd.
   • My further R&D activities were as Head of Chemistry in NasVax Ltd. a start-up company which aimed transformation of CCS to a drug product suitable for use with a variety of vaccines. The development of formulation and pre-clinical animal studies showed that CCS containing liposomes not only efficiently delivered vaccine antigen to Dendritic Cells (a class of antigen presenting cells triggering acquired immunity) and thus amplified the immunogenicity but, more important, efficiently protected animals (ferrets, which react to flu virus similarly to humans) challenged with live Influenza virus after immunization. These results were published, which resulted in collaboration with big pharma company Novartis. Unfortunately, Fase II clinical trials (humans) were inconclusive, probably due to unknown mechanism of action (MOA) and hence inability to recognize crucial differences between human and rodent and ferret immunity or/and probably due to inappropriate choice of the Influenza virus as an object since human adults frequently have pre-existing immunity to this virus (even though it rapidly mutates) and hence vaccine effect is not prominent.   

1. Summary of Current Research and Development Activities. I am currently involved in the research project "Antimicrobial peptide-sphingolipid conjugates" in collaboration with Dr. Zvi Hayouka from The Faculty of Agriculture, Food and Environment in the Hebrew University. The goal of this project is to develope new peptide-lipid conjugates possessing good antimicrobial activity and low toxicity to enable their potential application in pharma and food industry. The secondary goal is to develop effective liquid phase randomal peptide synthesis to reduce costs increase availability of antimicrobial peptides (AMPs). The project is partially supported by internal grant of JCT and the grant of Ministry of Agriculture.
2. Future Directions for Research and Development. After finding good AMPs candidates we plan to develop methods for coating polymers with such AMPs for potential application as antimicrobial packaging in food industry.

 (management positions over the past 15 years in small companies and the proprietary nature of projects in such companies have precluded many publications)

        Before latest appointment:

1. Books, Book Sections

2. Peer-Reviewed Papers in Refereed Journals

3. Rochlin and Z. Rappoport, Substituted xanthenylidene enols. The importance of -Ar-C=C conjugation in stabilization of aryl-substituted enols. J. Am. Chem. Soc. (IF 11.444, STR 6.317 Q1 Chemistry) 114, 230-241 (1992).

4. Eventova, E.B. Nadler, E.Rochlin, J. Frey and Z. Rappoport, The effect of tetra-m-bromo and tetra-m-methyl buttressing on the ground state structures, rotational barriers and keto-enol equilibria of 2,2-dimesityl-1-R (and 1-H) ethenols. J. Am. Chem. Soc., 115, 1290-1302 (1993).

5. Rochlin and Z. Rappoport, Mapping the enantiomerizattion routes of triarylvinyl propellers. Barriers for the 3-ring flip and the three different 2-ring flips of m-methoxy-substituted trimesityvinyl isopropyl ethers. J. Org Chem. (IF 4.638, STR 2.170 Q1 Organic Chemistry) 59, 3857-3870 (1994).

6. Rappoport, J. Frey, M. Sigalov and E. Rochlin, Recent advances in the chemistry of stable simple enols. Pure Appl. Chem.(IF 3.112, STR 1.172 Q1 Chemistry, Miscellaneous), 69, 1933-1940 (1997).

5.      Rochlin E, Rappoport Z, Kastner F, Pustet N, Mannschreck A., Four enantiomerization routes of 1,2,2-Trimesitylvinyl Acetate. Enantioselective Liquid Chromatography of (E)- and (Z)-2-m-Methoxymesityl-1,2-dimesitylvinyl Acetates., J Org Chem., 64(24):8840-8845 (1999).

6. Rochlin and Z. Rappoport, Stable simple enols. Resolution of chiral 1-[9’-(2’-fluoroanthryl)]-2,2-dimesitylethenol. A different racemization mechanism for the enol and its acetate. J. Org. Chem., 68, 216-226 (2003).

7. Rochlin and Z. Rappoport, Stable simple enols. Self-catalyzed E/Z isomerization of the sterically crowded 2-(m-methoxymesityl)-1,2-dimesitylethenol. J. Org. Chem., 68, 1715-1720 (2003).

8. Even-Or O., Samira S., Rochlin E., Balasingam S., Mann A.J., Lambkin-Williams R., Spira J., Goldwaser , Ellis R., Barenholz Y., Immunogenicity, protective efficacy and mechanism of novel CCS adjuvanted influenza vaccine. Vaccine (IF 3.485, STR 1.715 Q1 Medicine, Infectious Diseases), 28 (39), 6527-6541,(2010)

9. Orli Even-Or, Aviva Joseph, Noga Itskovitz-Cooper, Sarit Samira, Eli Rochlin, Hagit Eliyahu, Itzik Goldwaser, Shobana Balasingam, Alex J. Mann, Rob Lambkin-Williams, Eli Kedar, Yechezkel Barenholz., A new intranasal influenza vaccine based on a novel polycationic lipid-ceramide carbamoyl-spermine (CCS). II. Studies in mice and ferrets and mechanism of adjuvanticity. Vaccine, 29 (13), 2474-2486,(2011)

1. Peer-Reviewed Papers in Refereed Conference Proceedings

   1. Zvi Rappoport, Ella Nadler, Irena Eventova and Elimelech Rochlin, Recent advances in the chemistry of crowded aryl-substituted enols. Frontiers in Chemistry, 2nd TUB-Hebrew University Conference, Jerusalem, March 18-22, 1990, Abstr. p. 82

2. Elimelech Rochlin and Zvi Rappoport, Spontaneous enolization of 9-formyl and 9-aroyl xanthenes. The importance of -C=C conjugation in stabilization of triarylethenols. 10th IUPAC Conference on Physical Organic Chemistry, Haifa, August 5-10, 1990, Abst. A13, p. 27.

3. Zvi Rappoport, Irina Eventova, Elimelech Rochlin and Joseph Frey, Buttressing, isomerization and rotational barriers for several stable enols and derivatives.

                  Toronto International Conference on Organic Reactive Intermediates (TICORI), Scarborough College, Toronto, July 30-August 1, 1992. Abstr.

4. Zvi Rappoport, Elimelech Rochlin, Joseph Frey and Etti Schottland. Recent studies of intramolecular rotations of di- and tri-arylvinyl propellers. The 52nd Meeting of the Israel Chemical Society, Ramat-Gan, 17-18 February 1993, Abs. p. 41 (No page numbers in book).

5. Rappoport and E. Rochlin, Intramolecular rotations in substituted trimesitylvinyl propellers, 8th European Symposium on Organic Chemistry, Sitges, Spain, August 29 - September 3, 1993, Abstr. OCB-4.

6. Elimelech Rochlin and Zvi Rappoport, EZ Isomerization of crowded triarylethenols.

                  59th Meeting of the Israel Chemical Society, Beer Sheva, January 31-February 1, 1994, Abstract, p. 183.

7. Samira S., Joseph A., Goldwaser I., Rochlin E., Flasterstein O., Spira J., Barenholz Y. and Kedar E., Improved vaccines against influenza and other pathogens based on adjuvantation and delivery with a novel polycationic sphingolipid – CCS: Immunogenicity and efficacy studies in animal models, The 2^nd International Conference on Influenza Vaccines for the World, IVW 2006, Vienna, Austria, 18-20 October 2006

1. Patents  

2. Rochlin. Process for large scale preparation of sphingosines and ceramides.

                     US6,469,148, 22.10.2002, EP1187839, 20.03.2002, WO/2000/068238 09.05.2000

2. Barenholtz Y., Simberg , Rochlin E., Sphingolipids polyalkylamines conjugates, WO2004/110980, 23.12.2004, US7,771,711, 17.06.2004, EP1638919 17.06.2004

3. Rochlin, J. Hildesheim, A. Berlin, Sphingomyelin, intermediates thereof and methods for preparation of same, WO2005/068480, 28.07.2005, US7,687,652 13.01.2005, EP1704155 13.01.2005

                 Before latest appointment:

• 1993 Ben-Gurion Grant from the Ministry of Science, Research Fellow
• 2006-2010 Israeli Chief Scientist support for Industry. NasVax OCS project # 37399, 37602, 38802, 39104, 40289, 40819, 42074. The goal of this project was to develop the cationic liposome VaxiSome for adjuvanting vaccines and immunotherapeutics. Role: Chief Chemist
• 2010-2012 Israeli Chief Scientist support for Industry. NasVax OCS project #46556. The goal of this project is to develop Oral anti-CD3 monoclonal antibody (aCD3 MAb) immunotherapy for the treatment of inflammatory and autoimmune diseases. Role: Chief Chemist

1990-1993 – H.U., Instructor in Organic Chemistry Bet Lab., Advanced Organic Chemistry Lab. and in Physical Organic Chemistry training seminar.

Courses taught in JCT:

• 2002-2010 - Introduction to Chemistry, Introduction to Chemistry for Engineers
• 2006 – Organic Chemistry
• 2009 – 2011 – Organic Chemistry Bet, Organic Chemistry Gimel, Physical Organic Chemistry
• 2012-present – Organic Chemistry Alef, Organic Chemistry Bet, Physical Chemistry