Member Spotlights

Cutting Edge Chemistry at the Interface of Biomedicine, Nanotechnology and Targeted RNAi Therapeutics
Shyam Rele, Ph.D.
One of our newest Science Advisory Board Members.

Shyam Rele working in the lab.

This week The Science Advisory Board interviewed Shyam Rele, Ph.D., a Senior Scientist at Calando Pharmaceuticals. Rele's academic background includes Wilson College in Mumbai, India where he majored in Chemistry, the Bhabha Atomic Research Center (BARC) where he completed his Ph.D. in the Bio-Organic Division, and Emory University School of Medicine where he completed his post-doctoral work and was later appointed Assistant Professor. At Emory University, his extensive research involved, "problems related with vascular diseases, wound healing and tissue engineering (organ regeneration)", and allowed him to devise therapeutic methods from the multidisciplinary approach of medicine and chemistry. In 2006, this researcher decided to switch from academia to industry; he now works for Calando, a start-up biotechnology company focused on cancer therapeutics and nanomedicine. Rele is currently a member of the American Chemical Society, IUPAC, AAPS, and the Indian Chemical Society (of which he is a lifetime member). With his free time, Rele enjoys racquetball, ping pong, cooking, writing, photography and collecting books and old music. He also belongs to the Southern California Cricket Association League, where he's a team captain.

Please give us some insight into your academic and professional background.

I completed my BS and MS (University Merit Rank holder) from the old and reputed Wilson College, Mumbai with Chemistry as my major. This was followed by a short stint in academics as a Lecturer. However, my initial enthusiasm to make a living just out of teaching waned quickly. My interest in chemistry and my fascination to develop something new, something profound which someone has not explored or done before which would have societal benefits propelled me to join the field of scientific research. This urge to learn, improve, grow and expand resulted in me being selected by the Department of Atomic Energy for the prestigious Ph.D. program at Bio-Organic Division, Bhabha Atomic Research Centre (BARC), a Los Alamos equivalent atomic energy laboratory in Bombay, India. Under the tutelage of Dr A. Banerji, my research catered to two complete diverse fields of chemistry: synthetic organic chemistry and natural product chemistry (which was then sort of considered a dying branch of traditional chemistry research). As a synthetic chemist I was involved in the design and development of new and efficient reagents and reactions, methodology development and applications of organometallics in organic synthesis, new bond-forming and bond-breaking reactions (protection-deprotection strategies). These studies resulted in the invention of reactions of synthetic importance and led to a conceptual advancement in modern organic synthesis opening the fronts of many future scientific endeavors. On the other hand, the natural product chemistry work was directed towards phytochemical investigation of bioactive compounds such as secondary metabolites/growth hormones like 20-hydroxyecdysone, curcummin-based dietary antioxidants from ginger and protoberberine bioactive alkaloids.

The training, experience, expertise and the discipline gained during these formative years provided me with a solid foundation thereby enabling me to tackle future difficult and intricate problems at the interface of chemistry, biology, materials, medicine and nanotechnology.

The ability to generate and design desired new technologies, methodologies and molecules with novel and interesting properties has always fascinated me. On completion of my Ph.D., I joined Emory University School of Medicine (2001 – 2002) as a Post-Doctoral Fellow in the laboratory of Dr. Elliot Chaikof in the Department of Surgery and Bioengineering. In the short span of 4 years, I climbed up the academic ladder and was appointed as an Instructor (Oct 2003) and then Assistant Professor (Nov 2004).

Describe the post-doctoral research undertaken at Emory University.

My initial research at Emory catered towards addressing problems related with vascular diseases, wound healing and tissue engineering (organ regeneration). Since biological and medical sciences define most of the problems to be solved by chemists, I played a major part in a multidisciplinary initiative which involved the development of an advance generation of cardiovascular materials, devices, and pharmacotherapeutics based upon the principles of biomimetics, molecular engineering, and nanofabrication technologies. Efforts to achieve these goals within the framework of biomedical engineering and drug development required a multi-disciplinary approach and involved integrating and understanding the areas of polymeric materials, engineering, chemistry and medicine. In principle, my primary goal was to design and develop bio-inspired materials (peptide/protein based) and carbohydrate-based small molecules which will provide component building blocks for enabling advances in cell-based therapies, artificial organs, and engineered living tissues, all of which will define the evolving field of Regenerative Medicine. The following were the diversified project areas that I played a major role in (1) Carbohydrate-based anti-inflammatory agents targeted towards cardiovascular diseases; (2) Design and synthesis of cell surface carbohydrate mimetics such as Heparin/hyaluronan as modulators/inhibitors of signal transduction; (3) Generation of novel peptide-based materials (collagen) via self assembly for biomedical and nanotechnological applications; (4) Biomolecular engineering of membrane-mimetics and extracellular matrix components; (5) Multivalent scaffolding biomaterials, bioconjugates and novel drug delivery systems.

Carbohydrate-Based Drug Discovery and Receptor Targeting in Cardiovascular Disorders

One of the important domains of my work was to understand the role of sugars in vascular disorders such as inflammation and to design and develop carbohydrate-based ligand molecules capable of receptor binding and interrupting/blocking the biological chain of events associated with inflammation. Inflammation is a physiological response necessary for survival and is our body's first line of defense against injury or infection and plays an important role in the pathogenesis of many vascular diseases (such as aneurysms, atherosclerosis, angiogenesis, and thrombotic disorders). Characteristically, when tissue injury occurs, cytokines which are signaling proteins/peptides created by white blood cells, are released which signal or order the endothelial cells to synthesize selectins and to recruit leukocytes to the site of injury. When excessive leukocytes are recruited to the extravascular locations, normal cells are damaged leading to serious pathophysiological injuries causing acute and chronic inflammation. This adhesion of leukocytes to the stimulated vascular endothelium (which acts as a dynamic playground between blood elements and peripheral tissues), is a critical and a primary event of inflammatory response and triggers a cascade of complex multicellular processes. These processes are initiated by the early interaction between Selectin Adhesion Molecules and their clustered carbohydrate-containing ligands in a multivalent fashion. While significant effort has been directed towards generating sialic acid mimetics in various forms (small molecules, polymers, liposomes etc.), their relatively weak affinity (in millimolar range), susceptibility to hydrolytic cleavage, limited selectivity, potential antigenicity, short circulating half-life, and the absence of a convenient synthetic route are acknowledged limitations of such derivatized bioconjugates and other selectin inhibitors. As such, the development and synthesis of new and simpler therapeutic oligosaccharide analogues that can modulate selectin-mediated events resulting in the control of inflammatory disorders is a vigorously pursued area of much pharmaceutical interest. Consequently, blocking or interrupting the interactions between the selectins receptors and its physiologic ligands at an early stage of the inflammatory cascade by chemically synthesized carbohydrate entities on a biodegradable synthetic carrier such as polyethylene oxide (glycodendrimers) acting as “Synthetic Decoys” provides an effective way for developing anti-inflammatory agents to treat many acute and chronic inflammatory diseases.

To this end, I was successful in designing a glycosylation strategy to generate a sulfated glycodendrimer designated, SR-12, which was found to be among the most potent L-selectin inhibitors (IC50 = 2.4 nM) yet reported (based on in vivo and in vitro studies). Although heparin is known to inhibit inflammatory cell recruitment to a similar degree, concurrent anticoagulant effects limit heparin’s clinical applicability. In contrast, SR-12 did not exhibit any anti-thrombin activity. This observation was striking because a compound acting solely as a selective inhibitor of L-selectin was not anticipated to block in vivo leukocyte infiltration so completely. We therefore anticipate that SR-12, like heparin, may block chemokine binding to the endothelium, which would further restrict the leukocyte extravasation and accumulation and hence subsequently reduce the damage caused. As representative of a new class of selectin antagonist with high potency, we believe this compound warrants further investigation, particularly in a clinically relevant model of an inflammatory mediated disease. Such information may provide novel strategies for therapeutic approaches to the important problem of vascular disease. Significantly, the following thrust area to develop new anti-inflammatory strategies by in vivo blockade of selectin, limit thrombosis and reduce vascular inflammation was recognized and funded by the American Heart Association and Emory University Research Committee (2006).

Encouraged by these results, it prompted us to investigate the role of chemokines as inflammatory mediators in cardiovascular remodeling. In addition to selectins, chemokines too are known to play a crucial role in the recruitment of leukocyte to sites of inflammation. In this regard, our initial in vitro inhibition assay results using multivalent synthetic heparinoid dendrimer SR-12 with chemokine receptors is very promising and will further contribute to the understanding of GAG-chemokine interactions in cardiovascular diseases.

The prevalence and debilitating nature of chronic inflammatory diseases such as atherosclerosis, aortic aneurysm formation, and diverse vascular wall injury responses remains our number-one killer. While all these disease states are initiated, orchestrated, or otherwise modulated by local inflammatory responses, the underlying molecular and cellular mechanisms that eventually lead to a pathologic endpoint as a consequence of these stimuli remain largely undefined. We are currently exploring the critical role of polyvalent carbohydrate mimics as important regulators of tissue repair and local inflammatory responses in various animal models. By abrogating or downregulating (blocking) some of the inflammation-inducing players in the process, we will provide new strategies to decipher the factors affecting these processes.

All said, blocking or inhibiting the complex interplay between leukocyte, selectins, glycosaminoglycans (GAG’s), chemokines and matrix metalloproteases (MMP’s), as major culprits in the pathogenesis of vascular diseases may provide valuable targets for the design and development of new and efficient anti-inflammatory drugs and Selectin/Chemokine Antogonists/Inhibitors. I strongly believe that the present chemical approach provides the impetus to generate novel materials and drugs for effective applications as therapeutics in inflammatory, metastases or thrombotic disorders.

Glycosoaminoglycan/Proteoglycan Analogs as Modulators for Chemical Glycobiology

Cell surface carbohydrates such as glycosaminoglycans (GAG’s) and proteoglycans which ubiquitously decorate the cell surface are responsible for regulating and triggering a variety of pathophysiological processes such as coagulation, inflammation, metastasis, angiogenesis, cell growth, migration, and proliferation, and bacterial and viral recognition. However, many of the specific physiological activities that are mediated by these cell surface sugars, including heparin and hyaluronan, have not been completely defined due to their diverse and complicated structures and capacity to interact with numerous biologically active proteins. This is further complicated by the inherent complexity that has been associated with their direct chemical synthesis. Given the potential significance of therapies based on the control of GAG-protein interactions in various vascular disease states, one of the strategies I established was a structure based approach to devise versatile chemical strategies for the synthesis of cell surface oligosaccharides such as heparin- and hyaluronan-mimetics. The rationale here was to generate and identify smaller oligosaccharide sequences, which may be responsible for the unique biological activities of the parent cell surface carbohydrates. Such a chemical approach of generating synthetic derivatives of cell-surface GAG equivalents as modulators provides the ability to mimic and modulate specific receptor proteins interactions thereby regulating biomolecular recognition processes resulting in the identification of binding agonists and/or inhibitors.

Another strategy developed to understand the carbohydrate–protein interactions was to generate artificial glycopolymers. This has led to the efforts in which multiple copies of bioactive saccharide repeat units of glycosaminoglycan family members (hyaluronan and heparin sulfate) were attached on a stable polymer scaffold via chemical manipulations using polymer metathesis. We hope that such high affinity sugar ligands would provide additional impetus to understanding specific biomolecular recognition processes that hold relevance for both pharmaceutical and biomaterial applications. These and other analogues are under investigation for applications in controlled drug delivery and therapeutic angiogenesis.

I must mention here that, despite the central role of carbohydrates in various disease states, they have lagged behind peptides, proteins, lipids, and other compound classes as suitable drug candidates. Sugar chemistry as such is very demanding, challenging and at often times unforgiving. However, irrespective of the challenges posed in the post genomics and proteomics era, as old drugs become resistant and as new drugs, targets and diseases continue to emerge, I believe the present era will be dominated by the field of Glycomics where carbohydrate-mimics or glycoconjugates will play a defining role in understanding the genesis of various pathological disease states. I also strongly believe that sugar scaffolds will provide an unparalleled opportunity to generate libraries of high functional and structural diversity.

Chemistry-Intensive Efforts for Generation of Self-Assembling Synthetic Collagen and its Micro-Fibers in a Laboratory

One of the important components of the extracellular matrix is Collagen which comprises the major structural protein component of higher organisms. However, it remains a major challenge to emulate the unique structural and biological properties of native collagenous biomaterials in synthetic analogues. Consequently, numerous opportunities exist for synthetic collagens in biomedical applications as extracellular matrix analogues, if the appropriate materials could be constructed that retain and expand upon the desirable properties of native collagen fibrils. The exploration of chemical and molecular genetic techniques to design and synthesize collagen-mimetic polypeptides and fibers that are competent for self-assembly into structurally defined protein fibrils is an intriguing avenue for exploration. In this context, I have been leading the efforts in the de novo design of nanostructured biological materials through self-assembly of peptides and proteins. I have been successful in designing and synthesizing the first ever Synthetic Collagen Peptide system (36 amino acid units) which self-assembles into a fibrous structure with well-defined periodicity reminiscent of native collagen observed in our body. Specifically, the synthesized peptide protomer which is made up of three heterotrimeric peptide repeat units contains a hydrophobic proline-hydroxyproline core flanked on both the sides by distinct sets of peptide repeats containing either negatively (Glutamic acid) or positively (Arginine) charged amino acid residues. When positioned appropriately, these charged amino acids bias and adopt the triple helical self-assembly which undergoes fibrillogenesis at physiological temperatures producing D-periodic microfibers driven through electrostatic interactions.

This following discovery for making human collagen in the lab is pathbreaking in the field of nanotechnology and bio-inspired biomaterials. Several scientists for the past three decades have been trying to synthesize and emulate collagen's remarkable properties and have failed in their attempts to mimic the long, fibrous molecules found in nature. Our ability to generate a workable synthetic collagen in a laboratory (in vitro) on a nano-molecular level for the first time, therefore represents an important milestone in nanotechnology and biomaterial development. Such self-assembling peptides have broad applications in medicine, neurodegenerative diseases, protein folding catalyst design, bio-nanotechnology, tissue engineering and origins of life research. Furthermore, generation of such nanostructured molecules which mimic native structural proteins will lay the future ground work for unraveling complex phenomena including collagen fiber formation in protein conformational diseases and for the design of new materials with biological, chemical, and mechanical properties that exceed those of currently available synthetic polymers. The propensity of generating such self-assembling, biologically compatible peptide scaffolds to arrange themselves into fibers, tubules, and a variety of geometrical layers, establishes an important substrate for cell growth, differentiation, and biological function, and will have an important impact in the treatment of cardiovascular, orthodpedic, and neurological disease.

As a chemist, there is a tremendous sense of achievement and fulfillment for realizing the ultimate goal, which is to match and even emulate the behavior of biological systems and in creating and maintaining nanoscale structures with the same precision as that displayed by nature. This was a tremendously challenging project, but extremely satisfying and rewarding.

This work was recently published in the Journal of American Chemical Society ("D-Periodic Collagen-Mimetic Microfibers" by Rele et al, 2007, 129, 14780-14787) with exceptional peer reviews.

Development of Biomimetic Biomaterials and Scaffolds for Tissue Engineering and Reparative Medicine

Biomaterials and Tissue engineering are fundamental to the design and development of a wide variety of medical devices and implants. In addition, ongoing advances in understanding cell biology, wound healing, and targeted drug effects are creating opportunities for the use of biomaterials in unprecedented ways. While working in the Chaikof group, one of the research initiatives was to significantly improve the clinical usefulness of biomaterials by promoting and supporting research and development of novel biomaterials with improved biological and mechanical properties and new concepts and strategies for fabrication methods that can lead to biomaterials that are truly biocompatible and bio-responsive. Such projects involved a high degree of interaction and collaboration between engineers, chemists and biologists.

To this end, I was successful in designing and developing membrane-mimetic heparin-functionalized molecules which were immobilized on artificial blood contacting surfaces/organs to prevent or inhibit thrombus formation and improve hemocompatibilty during blood coagulation. The need for such surfaces in small diameter implantable medical devices such as arterial prostheses has become increasingly important due to the common use of polymeric implants in areas of the body where contact with moving blood is required, e.g., heart, blood vessels.

Furthermore, I was also actively involved in the development of collagen-based biomaterials for a number of tissue engineering and medical applications such as sealants, adhesion barriers, and scaffolds. There is a significant unmet medical need to develop new methods for enhancing the mechanical strength and durability of collagen. Photochemically active groups therefore introduced in collagen by chemical synthesis generated crosslinked sophisticated molecular biomaterials designed to achieve targeted functions to optimize construct stability and mechanical behavior.

What are your current research projects at Calando Pharmaceuticals?

In 2006, I made the transition from academia to industry and joined a start-up biopharmaceutical company Calando Pharmaceuticals, which originated from Prof. Mark Davis's lab at CALTECH, as a Senior Scientist. The primary research focus of Calando is research and development of Targeted cancer therapeutics and Nanomedicine using non-viral drug delivery platforms and RNAi technology. In addition, new targets, ligands and delivery systems for therapeutic intervention are also being developed.

RNA interference (RNAi) has been called “one of the most exciting discoveries in biology in the last couple decades", and the 2006 Nobel prize awarded to this relatively new field has further validated the significance of this powerful and young research field. RNA interference occurs in both plants and animals and plays a key role in mobilizing the body's defenses against infection, and in keeping unstable genes under control. In principle, RNAi uses short double stranded RNA (dsRNA) molecules whose sequence matches that of the gene of interest. Once in a cell, a dsRNA molecule is cleaved into segments approximately 22 nucleotides long, called short interfering RNAs (siRNAs). siRNAs are then bound to the RNA-induced silencing complex (RISC), which then also binds any matching mRNA sequence. Once this occurs, the mRNA is degraded by various enzymes, effectively silencing the gene from which it came. Given the ability to knockdown essentially any gene of interest, the science of RNAi has tremendous potential to revolutionize the whole way we think about biological processes and regulation.

One of the major challenges, however, which remains in this area, is to ensure efficient delivery of naked siRNA drugs to the diseased cells in living animals and eventually in humans. It requires the ability of intact siRNA to migrate through the body, reach diseased tissue, enter the cells and accumulate in therapeutically effective levels. To accomplish this, anionic siRNA’s are mixed with non-viral cationic polymers, which act as delivery systems resulting in the encapsulation of siRNA nucleic acid forming self-assembled spherical nanoparticles. The nanocarriers protect the siRNA from being degraded by enzymes inside the body. Once the target cells have been reached, the nanoparticles bind to specific receptors in the cell membrane, and the RNA-containing nanoparticle (nanocarriers) is taken into the cell by endocytosis. The in-built chemistry of polymer functions to release the siRNA from the delivery vehicle.

As a Senior Scientist at Calando, I am leading the initiative in designing, developing and modifying a panel of novel synthetic drug delivery technology platforms, bioconjugation strategies and targeted ligand development. I am also actively involved in the preclinical process and analytical development, evaluation and scaling-up operations of API and formulation/pre-formulation developmental activities.

My current research interests are synthetic non-viral drug delivery systems, targeted cancer therapeutics, RNAi, peptide and sugar-based ligand development, nanomedicine, carbohydrate-based drugs for vascular diseases, cardiovascular chemistry and anti-thrombotics, bio-inspired biomaterials, proteomics and new synthetic methodology and bioactive molecule development.

What were your motivations for pursuing this line of work?

The current scenario in industry and academia is such that biological and medical sciences define most of the problems to be solved by chemists. This acted as a great motivation for me, and life sciences provided me with the necessary playing field to create, experiment, understand, discover and innovate solutions for complex and intricate problems at a molecular level. Moreover, my broad research expertise in addition to my ability to utilize my core skills in an integrated fashion in close association with other disciplines was very critical in my being able to develop feasible solutions to the many interdisciplinary problems of our time that I was involved with, including the research work that I carried out at Emory.

With regards to my current research, while the RNA interference machinery is being unravelled at a frantic pace with the emergence of nanomedicine, it has opened up new possibilities for developing new therapies at chemical-biology, biomedicne and nanotechnology interfaces for the treatment of virus infections, cardiovascular diseases, cancer, endocrine disorders. This gives a researcher like me a real opportunity to use chemistry as a tool for developing therapies for various disease states including treatment of cancer which would have a direct influence in benefiting and improving human life.

In retrospect, has your career turned out as planned? How has your area of expertise evolved, and how have you adapted to those changes?

Scientific research is like climbing a mountain and has been and will remain a challenge. The question is, what do I do when I get to the top or when I achieve success? Some of us will still be climbing, and more than often, the failures encountered outnumber the success stories, while luck and serendipity too play an equally important role in this climb of a researcher. However, this climb has disciplined me and at the same time scientific research has made me appreciate the complexities of nature; as someone said, the universe is simple; it's the explanation that's complex.

From my own personal experiences, the role of chemistry in research has changed in the last few years and with that the role of scientist like me. In a short span of 5-6 years, I have been involved in cutting-edge research, both in academia and industry, and have contributed positively in my own little way to so many varied research fields from chemistry to biomaterials and drug design to nanotech and biomedicine. The dichotomy is such that while on a personal level this gives me an immense sense of achievement, satisfaction and intellectual fulfillment, philosophically on a larger scale it also makes me realize my responsibility and the bigger purpose that I need to serve for sociological relevance as a scientist.
All said, I don’t have any reason to complain since I love what I do, its been very gratifying and stimulating. The key to my motivation has always been to look at how far I had still to go rather than how far I had come. Importantly, more than a profession, scientific research has always been a passionate hobby for me, one of never-ending promises and possibilities, an adventure much of whose appeal is uncertainty and risk, ironically this personalized hobby of mine also happens to be the reason for my bread and butter.

What would you like to accomplish with future research efforts?

Research and education being intertwined, I would like to give back to the society the benefits of science and technology integrating research and education. Moreover, combining the pursuit of personal goals with sociological relevance is going to be a real challenge. I hope that in the future, using chemistry, I will able to achieve or contribute in my own small way to the therapeutics areas that I choose to work in and answer or understand some of the questions posed by the biomedical sciences.

What are your most notable achievements?

During my academic stay at Emory University School of Medicine, I was selected as one of the most Promising Early-Career Scientists by the American Chemical Society (ACS) to represent the United States in the bilateral U.S.-Indo workshop Advances in Organic Chemistry and Chemical Biology, held in India in January 2006. Conference invitations were limited to nine excellent early-career researchers (less than 45 years of age) from academia, industry and government in the United States to present and discuss their research in an international setting. I was one of only nine representatives from the United States, and at 32, the youngest, I presented my work on Glycodendrimeric Heparinoids: Synthetic Decoys for L-Selectin Inhibition and Anti-Inflammatory Agents. In 2006 – 2008, I received the American Heart Association (AHA) Beginning Grant-in-Aid Award for my proposal on suppressing Aortic Aneurysm Growth by Anti-Inflammatory Carbohydrates. In addition, in the same year, I was awarded the Emory University Research Committee Award (2006 – 2007). I was also a recipient of the Junior Research Fellowship and Senior Research Fellowship by the Department of Atomic Energy (DAE). In the recent months, I have been invited to be the Guest Editor for Current Bioactive Compounds and have also received an invitation to contribute to a review for Mini-Reviews in Organic Chemistry (MROC).

To discuss synthetic drug delivery platforms and other topics with fellow Science Advisory Board members, please visit our community forum.

The following are patents, publications, and presentations/abstracts by Rele and his colleagues that are relevant to this Member Spotlight.

Patents

Anti-inflammatory Glycodendrons. Shyam M. Rele, Wanxing Cui and Elliot Chaikof (Emory ID # 05046).
Patent Pending, available for licensing.

D-Periodic Collagen-Mimetic Microfibers. Shyam M. Rele, Elliot Chaikof, Vince P. Conticello.
Patent Pending, available for licensing.

Publications

Shyam M. Rele,† Y. Song, Z. Qu, R. P. Apkarian, V. P. Conticello and E. L. Chaikof. “D-periodic Collagen-mimetic microfibers.” J. Am. Chem. Soc., 2007 – In Press. FIRST REPORT
Shyam M. Rele,* S. Iyer and Elliot L. Chaikof. “Hyaluronan-Based Glycoclusters as Probes for Chemical Glycobiology.” communicated to Tetrahedron Lett., 2007, 48, 5055-5060.
Jeremy D. Heidel, Zhongping Yu, Joanna Yi-Ching Liu, Shyam M. Rele, Yongchao Liang, Ryan K. Zeidan, Douglas J. Kornbrust and Mark E. Davis. “Administration in non-human primates of escalating intravenous doses of targeted nanoparticles containing RRM2 siRNA.” Proc. Natl. Acad. Sci., 2007, 104, 5715-5721.
Elliot L. Chaikof, P. Tseng, Shyam M. Rele, S.W. Jordan and X. Sun. “Surface bound thrombomodulin and heparin inhibit tissue factor-induced thrombin generation in a flow model.” Journal of Surgical Research, 2006, 130, 203-204.
Po-Yuan Tseng, Shyam M. Rele, X-L. Sun and Elliot L. Chaikof. “Membrane-mimetic films containing thrombomodulin and heparin inhibit tissue factor-induced thrombin generation in a flow model.” Biomaterials, 2006, 27, 2637-2650
S. Jordan, K. Faucher, J. Caves, R. Apkarian, Shyam M. Rele, X.-L. Sun, S. Hanson, E. Chaikof. “Fabrication of a phospholipid membrane-mimetic film on the luminal surface of an ePTFE vascular graft.” Biomaterials, 2006, 27, 3473-3481.
Po-Yuan Tseng, Shyam M. Rele, Xue-Long Sun and Elliot L. Chaikof. “Fabrication and Characterization of Heparin- Functionalized Membrane-Mimetic Assemblies.” Biomaterials, 2006, 27, 2627-2636.
Shyam M. Rele,* W. Cui, L. Wang, S. Hou, G. Barr-Zarse, Daniel Tatton, Y. Gnanou, J. Esko, Elliot Chaikof. “Dendrimer-Like PEO Glycopolymers Exhibit Anti-Inflammatory Properties.” J. Am. Chem. Soc., 2005, 127, 10130-10131. Featured as Headline Alert article in Lead Discovery, DailyUpdates (www.leaddiscovery.co.uk).
C. Dong, J. Caves, Shyam M. Rele, B. Thomas and Elliot Chaikof. “Photomediated crosslinking of C6-cinnamate derivatized type I collagen.” Biomaterials, 2005, 26, 4041-4049.
Shyam M. Rele,* S. Iyer, S. Baskaran and Elliot Chaikof. “Design and synthesis of heparinoid mimetics.” J. Org. Chem., 2004, 69, 9159-9170.
U. Shadakshari, Shyam M. Rele,† S. K. Nayak and S. Chattopadhyay. Low-valent titanium mediated synthesis of hydroxystilbenoids: some new observations.” Indian J. Chem., 2004, 43B, 1934-1938.
S. Iyer, Shyam M. Rele,† Steven Nolan and Elliot Chaikof. “Synthesis of a hyaluronan neoglycopolymer by ring-opening metathesis polymerization.” Chem. Comm. 2003, 1518-1519.
S. Iyer, Shyam M. Rele,† S Baskaran and Elliot Chaikof. “Design and synthesis of hyaluronan mimetic Gemini disaccharides.” Tetrahedron, 2003, 59, 631-638.
Shyam M. Rele,† S. Iyer and Elliot Chaikof. “Homodimerization of hyaluronan and heparan sulfate derivatives by olefin metathesis reaction.” Tetrahedron Lett. 2003, 44, 89-91.
Shyam M. Rele,* A. Banerji, G. Chintalwar, V. Yadava and V. Kumar. “A new conformer (polymorph) of 20-hydroxyecdysone from S. portulacastrum. An X-ray crystallographic study.” Natural Prod. Res., 2003, 17, 103-108.
Shyam M. Rele and S. K. Nayak. “Investigation into low-valent titanium mediated reductive cleavage of O-trityl/N-trityl bonds via free radical pathway.” Synthetic Commun., 2002, 32, 3533-3540.
Shyam M. Rele,* A. Banerji, S. Talukdar. “Reductive amination of aliphatic carbonyls using low-valent titanium reagent: A convenient route to free amines.” J. Chem. Research (S), 2002, 253-254; J. Chem. Research (M), 2002, 619-626.
B. Patro, Shyam M. Rele,† G. Chintalwar, S. Chattopadhyay, S. Adhikari, T. Mukherjee. “Protective activities of some phenolic 1,3-diketones against lipid peroxidation: Possible involvement of 1,3-diketone moiety.” ChemBioChem, 2002, 3, 364-370.
Shyam M. Rele, S. Chattopadhay and S. K. Nayak. “Highly active salted low-valent titanium reagent for various SET-induced reactions.” Tetrahedron Lett., 2001, 42, 9093-9095.
Shyam M. Rele, S. Talukdar, A. Banerji and S. using Chattopadhay. “Generation of reactive low-valent titanium species metal-arenes as efficient organic reductants for TiCl3: Applications to organic synthesis.” J. Org. Chem., 2001, 66, 2990.
Shyam M. Rele, S. Talukdar and A. Banerji. “A facile radical induced selective removal of N-propargyl protecting groups using LVT reagents.” Tetrahedron Lett., 1999, 40, 767-770.
J. N. Dhuley, S. R. Naik, Shyam M. Rele and A. Banerji. “Hypolipidaemic and antioxidant activity of diallyl disulphide in rats.” Pharmacy and Pharmacology Communications, 1999, 5, 689-696.

Selected Presentations/Conference Proceedings/Abstracts

Jeremy D. Heidel, Yi-Ching Liu, Zhongping Yu, Yongchao Liang, Shyam Rele, Yun Yen and Mark E. Davis, “Development and in vivo tolerability testing of a therapeutic formulation containing siRNA against the M2 subunit of ribonucleotide reductase in mice and monkeys.” American Association for Cancer Research Annual Meeting, Los Angeles, CA, April 14-18, 2007.
Shyam M. Rele and E. L. Chaikof, “Multivalent sulfated PEO glycodendrimer. A highly potent L-selectin binding antagonist.” Presentation: at 231st ACS – Spring Meeting, Atlanta, Mar 26-30, 2006.
Shyam M. Rele, S. Iyer and E. L. Chaikof, “Glycosoaminoglycan oligosaccharide derivatives: Versatile intermediates and synthetic potential.” Presentation: ACS – Spring Meeting, Anaheim, Mar 16-19, 2004.
Shyam M. Rele and Elliot Chaikof, “Sugar-coated opportunities and potential of glycosoaminoglycan oligosaccharides.” Poster: 8th Annual Hilton Head Workshop, Cardiovascular Tissue Engineering: From Basic Biology to Cell-Based Therapies, March 6-10, 2004.
Shyam M. Rele and Elliot Chaikof, “Design and development of artificial multivalent glycoconjugates to study biomolecular recognition.” Presentation: at 55th Southeast Regional Meeting of ACS (SERMACS), Atlanta, Nov 2003.
Shyam M. Rele, Po-Yuan Tseng, Suri Iyer and Elliot Chaikof, “Strategies for design and development of engineered glycomimetics, carbohydrate-based scaffolds and biomimetic materials.” Presentation: Bioinspired Biomaterials, Georgia Tech. Centre for Engineering of Living Tissues, Aug 19, 2003, USA.
Shyam M. Rele, S. Iyer and Elliot Chaikof, “Carbohydrate-based mimetics in drug discovery and bioengineering.” Presentation: NSF Site Visit (5th Year), Georgia Tech/Emory Centre for Engineering of Living Tissues, April 1-2, 2003.
Shyam M. Rele, S. Iyer and Elliot Chaikof, “Target-oriented design and synthesis of structurally defined small-molecule glycomimetics.” Presentation: Glycoconjugates XVII, International Symposium on Glycoconjugates, IISc, Bangalore, Jan 12-16, 2003, India.
S. Iyer, Shyam M. Rele, S. Baskaran and Elliot Chaikof, “Design and synthesis of well-defined oligomeric assemblies of hyaluronan.” Presentation: 223rd ACS Meeting, Boston, Aug 2002.
S. Iyer, Shyam M. Rele, S. Baskaran and Elliot Chaikof, “Design and synthesis of Hyaluronan-mimetic glycopolymers.” Poster: at the Gordon Conference Proteoglycan 2002, Proctor Academy, New Hampshire, July 2002.
L. Nair, K. Trivedy, Shyam M. Rele, G. J. Chintalwar, P. K. Chinya, R. K. Dutta, S. Chattopadhay, A. Banerji. “Ecdysteroid from S. portulacastrum for synchronization of cocoon spinning in silkworm B. mori.” Proceedings Chapter: Adv. Indian Sericulture Res., Proc. Natl. Conf. Strategies for Sericulture Res. and Develop., Ed: S. B. Dandin, V. A. Gupta, 2002, 247-251.
U. Shadakshari, Shyam M. Rele, M. Kumar and S. K. Nayak, “Structure –antioxidant activity studies of some synthetic hydroxy stilbenioids.” Poster: International Conference on Natural antioxidants and Free Radicals in Human Health & Radiation Biology (NHFR-2001), July 21-24, 2001 (P21-16, p 226), BARC, Mumbai.
L. K. S. Nair, Kanika Trivedy, Shyam M. Rele, G. J. Chintalwar, P. K. Chinya, R. K. Datta, S. Chattopadhyay and A. Banerji, “Ecdysteroid from Sesuvium portulacastrum for synchronization of cocoon spinning in silkworm Bombyx mori.” Conference proceeding: SWPP/O3, Mysore, 2000, Pg 62.
Shyam M. Rele, Sanjay Talukdar, S. K. Nayak and A. Banerji, “LVT-induced SET reactions: Influence of chemical redox agents & external additives on the McMurry reaction.” Presentation: International Conference on Chemistry at 36th Annual Convention of Chemists 1999 (Platinum Jubilee Celebration), Indian Chemical Society, Calcutta University, Calcutta, Dec 1999.
Shyam M. Rele, Sanjay Talukdar and A. Banerji, “Reductive amination of carbonyls using Low-valent Titanium Induced directed Cleavage of Carbon-Heteroatom Bonds.” Presentation: 35th Annual Convention of Chemists, Indian Chemical Society, Karnataka University, Dharwad, Nov 1998.

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