Welcome to Dr.P. Rathanaswami's Webpage
 

Major Researches

My research interest started by studying the mechanism of insulin secretion in malnutrition way back in 1980's. From endocrine research my interest slowly shifted to molecular endocrinology, inflammation immunology and arthritis.

 

Later my focus changed to work on antibody engineering where i was involved in generating a number of human antibodies for various diseases. I continue to work in this field till now.

 

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MY RESEARCH JOURNEY

 

Apr 2006- Present

 

 

 

 

Scientist, Amgen British Columbia (ABC), Burnaby, CANADA. Reporting to Senior Director.(Abgenix was acquired by Amgen in April 2006)

§         Senior Team Leader in the site. Leading many antibody generation projects, leading the Kinetic analysis and molecular biology groups. Leading antibody effector function improvement projects.

 

Nov 2000- April 2006

 
 

Senior Scientist/Scientist, Abgenix Biopharma Inc., Burnaby, CANADA. Reporting to Associate Director/Director.

§         As a senior team leader, I managed the projects connected to the generation of human monoclonal antibodies from Xenomouse using SLAM technology (around 20-25 projects per year) for Abgenix and its partners.

§         Successfully implemented an easy and efficient system for cloning and expression of human antibodies.

§         Worked with bioinformatics team and developed a high throughput human antibody sequence analysis and annotation system.

§         Mentored the group, consisting of Junior Scientists and Research Associates, to analyze and document the sequences for patent filing.

§         Worked with off-site Scientists to select projects, define time lines, and successfully met the time lines.

§         Developed a method to measure the affinity of antibodies in sub-picomolar range and supervised Junior Scientists to successfully complete the measurement of affinities for several antibodies.

§         Developed methods to measure the affinity of antibody to membrane-expressed antigens and native antigens available only at picogram quantities. Leader for developing monoclonal antibodies to a tumor target.

§         Lead the project from immunization of Xenomice, generating antibodies, preclinical in vitro and in vivo characterization and up to patent filing.

§         Abgenix leader for generation of antibodies for two of the tumor targets for Abgenix's partners.

§         Working closely with the Scientists of Abgenix's partners to generate human antibodies using Xenomice according to the mutually defined design goals and timeline.

§         Member of the Abgenix Biopharma management team and Animal Care Committee.

§         Abgenix Biopharma's Chemical Safety Officer and Chair of Safety committee.

 

1998- Nov 2000

 
 

Research Scientist, ImmGenics Pharmaceuticals Inc., Vancouver, CANADA. Reported to CEO and President. (ImmGenics was acquired by Abgenix in Nov 2000).

·         Team leader for the single cell RT-PCR amplification, cloning and expression of rabbit and macaque monoclonal antibodies.

·         Directed the team to generate antibodies for several projects (7-10 projects per year) involving efficient expression of rabbit and macaque monoclonal antibodies.

·         Directed the group to sequence all the antibodies amplified in the lab, analyze and annotate them and generate database for each species of antibodies.

·         Supervised a team that is responsible for the high affinity measurements of the generated antibodies (at least five different antibodies per project).

·         Involved in the recruitment of employees, new employee training and development.

1993- 1998

 
 

Research Associate, Biomedical Research Centre, University of British Columbia, Vancouver, CANADA.

Project: Generation of Human monoclonal antibodies for therapy by a novel technology.

 

·         One of the four lead members of a team, which developed, “Selected Lymphocyte Antibody Method” (SLAM) for the generation of human monoclonal antibodies.

·         Responsible for developing single cell RT-PCR amplification of human Immunoglobulin V regions, cloning and their expression as recombinant antibodies.

·         Mentored and supervised one research technician and several co-op students for cloning and expression of antibodies.

·         Generated antibodies for three different targets (tetanus toxin, human influenza and human CMV) from single human B cells using SLAM technology, expressed as recombinant human monoclonal antibodies.

·         Characterized a number of anti-tetanus toxin antibodies for their efficacy in neutralizing the toxin in-vivo in animal models.

·         Developed the solution binding kinetic assays using KinExA and measured the affinities of several very high-affinity (low picomolar range) antibodies.

1992- 1993

 
  Research Associate, Inflammation and Immunology-Rheumatology Research Unit (IIRRU), Le Centre Hospitalier de l'Universite Laval (CHUL), Laval University, Quebec, CANADA.


Project: Effect of cytokines on the differential regulation of chemokine gene expression in human rheumatoid synovial fibroblasts

     
1990 -1992
 

Postdoctoral Fellow, IIRRU, CHUL, Laval University, Québec, CANADA.


Project: Analysis of chemokine gene expression in human rheumatoid synovial fibroblasts.

·         Studied the gene regulation and expression of chemokines including Interleukin-8, RANTES, MCP-1 and MCP-2, in human rheumatoid synovial fibroblasts and neutrophils.

·         Have shown that the chemokines of the PF4 superfamily are differentially upregulated in synovial fibroblasts depending upon the stimuli.

·         Showed that the amount of C-X-C and C-C chemokines produced at the site of inflammation, by the fibroblasts, depends on the nature of the monokines and lymphokines to which these fibroblasts are exposed and the type of leukocyte infiltrated into the inflammatory site could be controlled by the nature of the existing cytokine/chemokine stimuli. Also showed that the neutrophils accumulate at the site of acute inflammation are capable of releasing more IL-8 and hence could induce an autocrine response. Glucocorticoids have differential effect on the transcriptional and post-transcriptional regulation of each of these genes.

·         Involved in cloning and sequencing promoters of some of these chemokine genes.

I have six publications from this work.

1989 - 1990  
 

Postdoctoral Fellow, Molecular Endocrinology Lab., CHUL, Laval University, Québec, CANADA.

Project: Cloning the steroid hormone receptor genes, study their regulation and expression.

·         Successfully cloned a transcription factor that binds to the promoter region of the human glucocorticoid receptor gene and represses the expression of glucocorticoid receptor.

·         Acquired training on cloning and sub-cloning of genes, screening cDNA libraries, mapping the genes, and expressing cDNAs as fusion proteins. Using chimeric steroid receptor gene constructs, conducted considerable gene transfer studies. Studied the expression and regulation of steroid receptor genes by introducing chimeric genes into mammalian cells.

The above findings contributed to publication of three publications in leading peer reviewed journals.

1982 -1988  
 

Ph.D., University of Madras, INDIA.

 

Title: “Effects of tolbutamide and glucose metabolism on the functions of beta cells of the pancreas in rats”.

·         Studied the effect of thiamine deficiency (TD) on the secretion and synthesis of insulin. Unlike in the developed countries, where over nutrition is the main cause for nutritional disorders, in developing countries including India, malnutrition causes a variety of disorders. On this basis, thiamine deficiency was selected for the study. The effect of thiamin deficiency on the endocrine functions of the pancreas was studied in vitro and in vivo in a rat model. Part of the study was also performed on isolated pancreatic islets.

The study led to the following crucial findings:

1) Glucose tolerance was impaired in thiamine-deficient rats.

2) Even though the fasting blood glucose was high in TD, the fasting serum insulin levels were low, suggesting that the synthesis and/or the secretion of insulin from pancreatic islets were certainly affected.

3) The in vivo insulin synthesis in response to tolbutamide administration was low in TD.

4) In the isolated rat pancreatic islets, the insulin secretion, the metabolism of glucose, and the response of thiamine-deficient islets to the administered glucose and tolbutamide were impaired.

5) Malnutrition also could cause diabetes by impairing the glucose metabolism in the islets of Langerhans.

The above findings led to four publications.