· Selected Peer-Reviewed Publications
XXX
(3) The impact of Dr. __XXX__’s articles has been demonstrated by citations in independent journals. His work has been cited by publications in a variety of peer-reviewed international journals and proceedings.
Dr. __XXX__’s publications have provided very important leading data and information for research and development in the fields of biomedicine, vaccination and immunology of infectious disease and cancer prevention, particularly in atherosclerosis, pathogenesis of TB, vaccination development for TB, innate immunity of HIV, HIV microbicide development and the study of the mechanism of anti-tumor drug I3C. Some of Dr. __XXX__’s publications have been cited widely in a variety of prestigious peer-reviewed journals by many national and international research groups at universities, research institutes, and governmental agencies such as University of Tennessee, TN, USA, Montana State University, MT, USA, Turner Enterprises Inc, MT, USA, etc.
(4). Dr. __XXX__’s exceptional research ability has enabled his to become a member of associations requiring significant contributions in the field.
Due to his breakthrough achievements in the fields of biomedicine, vaccination and immunology of infectious disease and cancer prevention, Dr. __XXX__ has become a member of the American Association for the Advancement of Science (AAAS) and the New York Academy of Science (NYAS). (See Exhibits 29-30)
Exhibit 29: A copy of membership card of the American Association for the Advancement of Science (AAAS)
Exhibit 30: A copy of membership card of the New York Academy of Science (NYAS)
(5). Dr. __XXX__’s unique ability for novel discoveries, broad experience and outstanding contributions to the areas of biomedicine, vaccination and immunology of infectious disease and cancer prevention have been highly recognized by well-known experts as exceeding others in his profession and distinguished his from others.
Throughout his past more than thirteen (13) years of research career, Dr. __XXX__ has consistently demonstrated his exceptional talents and ability. Dr. __XXX__ has successfully performed several challenging biomedical research projects of atherosclerosis, pathogenesis of TB, vaccination development for TB, innate immunity of HIV, HIV microbicide development and the study of the mechanism of anti-tumor drug I3C. With his unique ability and extensive research experience in these areas, Dr. __XXX__ has made several innovative discoveries, which have opened new avenues for the US public health -related research. This immigrant petition is based on the unique and unusual expertise of Dr. __XXX__ who clearly exceeds others in his profession and has advanced the field. His expertise truly benefits the national interest and presents significant impact on the American healthcare, the improvement of national environment. Retaining Dr. __XXX__ in the US and the approval of his petition are in the US national interest. The following testimonies from well‑known experts and established U.S. institutions attest the importance of Dr. __XXX__’s research and his significant impact and role in the research. Some testimonial letters are from the experts and professors totally independent of Dr. __XXX__.
(1) Dr. XXX, the Chief of Infectious Disease Division, and a professor of Medicine and Associate professor of Microbiology at XXX School of Medicine (MSSM), attested: “Dr. __XXX__ discovered that bacterial cell wall components lipopolysaccaride (LPS) and lipooligosaccaride (LOS) could delay the infectivity of HIV-1 to human macrophages and CD4 T cells dramatically in a low dosage. … This phenomenon is the first time being observed by Dr. __XXX__ and it has deep impact on the research on the interaction of bacterial LPS and LOS to HIV virus. Further research in this direction can not only enhance our knowledge about innate immunity to HIV, but also have dramatic influence on a new aspect to the HIV drug development. Therefore, whether Dr. __XXX__ can study steadily and long on this project is very critical for the success of this project and also the interest of our nation in a long run.
… Dr. __XXX__ has observed that supernatants of Chlamydia infected vaginal and ectocervical cells induced the expression of latent HIV in human macrophage cell line U1. Though some cytokines, such as TNF-a, IL-6, and IL-1, exist in the supernatant, they are not the only factors for the induction of latent HIV because antibodies for these cytokines cannot totally block the effects of the supernatants on the reactivation of HIV. This project is a governmentally sponsored research on interaction of bacteria on HIV infection, and Dr. __XXX__ has become a key member for this study.
… Dr. __XXX__ has set up a stable model to detect the reactivation of latent HIV in U1 cell that will be used efficiently to screen the efficacy of different dosage and combination of microbicides with other anti-HIV drugs.
… Dr. __XXX__’s work and experience have elevated his well above the majority of his colleagues in biomedical research. Based on my twenty years of professional career, I have no doubt in my mind that Dr. __XXX__ is the type of resources that should be utilized for HIV research in the United States. A person like his has a lot to offer in developing a long-term solution to the nation's HIV infection. …” (See Exhibit 4)
Exhibit 4: Testimonial letter from Dr. XXX, the Chief of Infectious Disease Division, and a professor of Medicine and Associate professor of Microbiology at XXX School of Medicine (MSSM)
(2) Dr. XXX, Professor of pathology and honorary director in Institute of Basic Medical College (IBMC), Chinese Academy of Medical Sciences and Peking Union Medical College (Beijing, China), testified: “Dr. __XXX__ originally and successfully set up the model of atherosclerosis using New Zealand rabbits. De-endothelialization with balloon angioplasty and high-cholesterol diet make rabbits to develop atherosclerosis in six weeks. Administration of simvastatin and gemfibrozil showed significant decrease of total cholesterol and triglyceride level in serum and the neointimal formation in our atherosclerosis rabbit model. Two growth factors, platelet-derived growth factor-B (PDGF-B) and transforming growth factor b1 (TGFb1) were inhibited in protein and mRNA levels. This indicated that lipid lowering drugs, simvastatin and gemfibrozil, may inhibit the release of PDGF-B and TGFb1 in neointima after de-endothelialization. Dr. __XXX__ opened a new avenue to the understanding of the molecular mechanism of lipid-lowering drugs, and his work was published in a professional peer-reviewed journal Chinese Medicine Journal (2001).” (See Exhibit 9)
Exhibit 9: Testimonial letter from Dr. XXX, Professor of pathology and Honorary Director in Institute of Basic Medical College (IBMC), Chinese Academy of Medical Sciences and Peking Union Medical College (Beijing, China)
(3) Dr. XXX XXX, Professor and Program Director of Pathology at New York Medical College, affirmed: “Dr. __XXX__ has played a critical role in developing and carrying out three projects sponsored by United States National Institutes of Health and the Belgian (Flemish) Medical Research Council and has made major and significant contributions to their successful completion. These projects are: 1) identifying a novel regulatory DNA element in the Mycobacterium tuberculosis genome and in other pathogenic mycobacteria; 2) using this element to improve foreign gene expression in recombinant BCG far use in novel anti-prostate cancer vaccines and and in other mycobaeteria to produce recombinant mycobacterial proteins for development of new drug targets for antimicrobial agents; 3) using monoclonal and poiyclonal irrnnunoassays to detect elevated levels of mycobacterial proteins in the circulation of patients with active tuberculosis as a novel method for rapid diagnosis of this disease.
Dr. __XXX__’s exceptional knowledge in different branches of microbiology and his unique skills in molecular biology have been critical to all these projects. His research findings have been presented in an original research article published in Journal of Clinical Microbiology, an internationally recognized, peer-reviewed journal with international circulation. Two additional manuscripts are currently under review and a fourth manuscripts in preparation for publication in other internationally recognized peer-reviewed journals. Dr. __XXX__ has presented his work at international and national conferences, such as the 38th United States-Japan Research Conference on Tuberculosis and Leprosy, Newark, N. .1. (2003), the 103rd general meeting of American Society for Microbiology in Washington, D.C. (2003), and the 4th Annual New York City TB Conference in New York, N.Y. (2002). Two patents based on Dr. __XXX__’s inventions have been filed by New York Medical College. In recognition of his abilities and interests, Dr. __XXX__ was accepted as a member of American Society of Microbiology in 2003.
The research projects to which Dr. __XXX__ contributed especially and significantly are described below:
1. … Dr. __XXX__’s original work successfully identified and experimentally proved that a highly repetitive sequence rptl in the genome of Mycobacterial tuberculosis H37Rv contains enhancer activities for rnycobacterial gene expression. Dr. __XXX__’s pioneering work has therefore enriched our understanding of the molecular pathogenesis of tuberculosis and can be expected to have a long-term impact for many areas of tuberculosis research here in the United States and throughout the world.
2. Based on his discovery of this mycobacterial gene regulatory DNA element, Dr. __XXX__ developed novel expression vector plasmids containing this element for efficient expression of foreign proteins in mycobacterial cells. He has used his system to express a humanprostate cancer marker protein, prostate specific antigen (PSA), in large quantity for use as an anti-cancer vaccine. The idea of application ofBCG as vaccine against cancer specific antigen and thus to prevent tumor metastases is still in the early stage. However, Dr. __XXX__’s work has already offered a practical tool for tumor immunotherapy. Furthermore, in vitro expression of proteins from virulent mycobacteria in harmless niycobacteria could permit production of many more proteins in more native structures than are currently possible using Eschcrichia ccili, the current standard system for these studies. The available of Dr. __XXX__’s all mycobacterial system for mycobacterial protein production is a major step forward and can again be expected to have important future benefits for patient health both in the United States and worldwide.
3. … Dr. __XXX__ played an important part in developing this test using monoclonal antibodies binding to a major mycobacterial secretary protein (Ag85) found in the circulation of patients with tuberculosis and using this test to show that it was an appropriate diagnostic assay for tuberculosis that did not depend on the patient having an intact immune response. It can be expected that this novel diagnostic assay for tuberculosis, the development of which Dr. __XXX__ has made a major contribution, will also prove to be a major contribution to public health in the United States and worldwide.
I have been impressed by Dr. __XXX__’s exceptional knowledge of microbiology and vaccinology and his devotion to human health sciences. His creative, well-organized work and the integration of his solid microbiological background with his expertise in human health research can be expected not only lead to efficient solutions of current infectious diseases, but also to put his in the frontline of these research areas.” (See Exhibit 13)
Exhibit 13: Testimonial letter from Dr. XXX P. Godfrey, Professor of and Program Director Pathology at XXX XXX Medical College
(4) Dr. Raj K. Tiwari, Graduate Program Director and Associated Professor in the Department of Microbiology and Immunology at New York Medical College, highly commended: “Dr. __XXX__ has made internationally recognized significant contributions to infectious diseases and cancer research like the discovery of a mycobacterial gene regulatory DNA element, study of mechanism of anti-tumor compound antiestrogen indole-3-carbinol (I3C) and the regulation of heat shock protein gp96 by cytokine IFN-g and IL-2. These contributions have brought, and will also bring substantially and intrinsically important benefits to the tuberculosis and cancer research. As his co-mentor and an expert in Dr. __XXX__’s research areas, I strongly believe that Dr. __XXX__ is a scientist of exceptional abilities in the field of biomedical science and his significant accomplishments have impacted these research areas significantly. I believe the United States will greatly benefit if Dr. __XXX__’s petition for permanent residency is granted.
… Dr. __XXX__ has been taking a leading part in the investigation of cellular target proteins by I3C in estrogen positive breast cell lines. His results indicated that I3C exerts its antiestrogenic effect by intervention in the E2-estrogen receptor signal transduction pathways, which includes several DNA binding element, such as AP2 and SP1. Also, gene array data showed that biochemical targets of I3C could be multiple and more than the estrodiol-medicated functional proteins. Dr. __XXX__’s results enlarged our understanding of chemoprevention compound I3C and published in two peer-reviewed articles in European Journal of Cancer Prevention (2002) and Nutrition and Cancer (2001). Dr. __XXX__ also presented these data at the 94th and 95th Annual Meetings of American Association of Cancer research in 2001 and 2002 respectively.
… Dr. __XXX__ performed electrophoresis mobility shift assay to recognize the induced transcription factors that enhanced gp96 level under the treatment of IFN-g and IL-2. Interferon-activation sequence (GAS) located in the promoter region of gp96 showed increased binding to nuclear proteins and STAT1 protein, a classic transcription factor for GAS also has correlated increase. These results reveal a possible link between the IFN-g and IL-2 to the enhanced expression of gp96 through the interaction of STAT1 protein with GAS DNA element. It also offered a theoretical basis for cancer immunotherapy using gp96 as a bridge. A paper reporting all these data has been published in Cell Stress and Chaperone in 2003.
In addition, Dr. __XXX__ also made a successful work on ‘Regulation of Gene Expression by a Novel Mycobacterial Repetitive DNA Sequence’”. (See Exhibit 19)
Exhibit 19: Testimonial letter from Dr. XXX, Graduate Program Director and Associated Professor in the Department of Microbiology and Immunology at XXX Medical College
(5) Dr. XXX, the Chief and Associate Professor of Pediatric Infectious Diseases, Department of Pediatrics, XXX School of Medicine, pointed out: “Dr. __XXX__ established himself as an expert in the field of biamedicinul research, particularly in the research areas of microbiology, vaccination and cancer research. He investigated the molecular pathogcncsis of Mycobactertsm lubercwlosis by identifying a novel gene regulatory DNA element, rptl. rptl is a highly repetitive DNA element in the gcnome of Mycobactertal tuberctrlosis H37Rv. When introduced into mycobacterial expressive vector, rptl works as a promoter and an enhancer for the expression of reporter gene. A new recombinant BCG was also generated based on Dr. __XXX__’s study of rptl. In this novel vaccine, a foreign gene can be expressed effectively in BCG celln. Two manuscripts and a patent have been submitted on this project. Dr. __XXX__ also presented his work at several national and international meetings including the annual meeting of American Society of Microbiology, US-Japan cooperative medical science program, the 38th Tuberculosis and Leprosy research conference, and others.
... Dr. __XXX__ made quick contribution to this project by finishing the IL-6 and TNF-a blocking experiment. This work will be present in the 42nd Annual Meeting of the Infectious Diseases Society of America in 2004.” (See Exhibit 24)
Exhibit 24: Testimonial letter from Dr. XXX XXX, the Chief and Associate Professor f Pediatric Infectious Diseases, Department of Pediatrics, XXX School of Medicine
(6) Dr. XXX XXX, Member of the National Academy of Sciences, Research Professor Emeritus, Dept. of Microbiology and Immunology at New York Medical College, attested: “Dr. __XXX__ has distinguished himself as a prominent biomedical researcher by his original and crucial contributions to the biomedical research area and his current indispensable role in an NIH funded research project on HIV. His achievements set his apart from many other individuals in similar and related fields of research. I firmly believe that Dr. __XXX__ is a highly competent and creative member of the biomedical community and he will continue to make important contributions to infectious diseases research area, which have benefited and will prospectively benefit US healthcare and economy, a recognized national interest.
… Dr. __XXX__ is a scientist with unique expertise in the field of tuberculosis pathogenesis and vaccination. He experimentally proved that a highly repetitive mycobacterial DNA element, rpt1, has specific binding with proteins from the lysates of BCG, Mycobacterium tuberculosis, and Mycobacterium smegmatis.
… Dr. __XXX__’s work has been reported in the 103rd annual meeting American Society of Microbiology and 38th Tuberculosis and Leprosy research conference, US-Japan cooperative medical science program.
Dr. __XXX__ is now working as a research scientist in Infectious Diseases Division, Department of Medicine, XXX School of Medicine. He applies his experience in tuberculosis to HIV research and focus on the innate immunity with HIV infection. As a newly developed life-threaten infection, HIV significantly affects our society physically and morally. The research of HIV infection is far from needed, especially the immune response to HIV virus, which is the basis for HIV treatment and prevention. Dr. __XXX__ has found that low dosage of lipipolysaccharide and lipooligosaccharide can delay the HIV infection to the human macrophage and CD4 T cells. This phenomenon opens a gate to a new field in understanding the immune response to HIV and potential HIV treatment.” (See Exhibit 31)
Exhibit 31: Testimonial letter from Dr. Edwin D. Kilbourne, Member of the National Academy of Sciences, Research Professor Emeritus, Dept. of Microbiology and Immunology at New York Medical College
(7) Dr. XXX XXX, Dean of the Graduate School of Basic Medical Sciences and Professor of Physiology at New York Medical College, wrote: “His (Dr. __XXX__’s) doctoral dissertation focused on tuberculosis, a major health problem in the United States and worldwide. His research identified a regulatory clement in the tuberculosis bacterium that appears to be important in the pathogenesis of this organism. It may also provide a target for a workable tuberculosis vaccine, for which Dr. __XXX__… filed a patent application. More recently, he has been working on the human immunodeticiency virus (H1V).
Dr. __XXX__’s productivity as a scientist is already apparent, despite his relatively young age. He produced usable research results within mere months of beginning graduate school, and has already produced two research reports in the first six months of his post-doctoral appointment. He has already filed two patent applications, further demonstrating his scientific creativity.
… Dr. __XXX__ is a is an enthusiastic and talented researcher, whose unique and noteworthy work in the field of infectious disease and other field in biomedicine has and will benefit the health research of United States….” (See Exhibit 32)
Exhibit 32: Testimonial letter from Dr. Francis L. Belloni, Dean of the Graduate School and Professor of Physiology of Basic Medical Sciences at New York Medical College
(8) Dr. XXX XXX, Professor and Vice–chair for Researcg, Department of Medicine, UMDNJ Center for BioDefense at XXX Medical School, NJMS-National Tuberculosis Center, confirmed: “Dr. __XXX__ was the first scientist to successfully perform electrophoresis of mobility shift to show that rpt1 has specific binding with mycobacterial proteins from BCG, Mycobacterium tuberculosis, and Mycobacterium smegmatis. Then, he initially introduced rpt1 tandem into a mycobacterial expression vector. The rpt1 tandem increased the expression reporter gene when introduced between original promoter and reporter gene or replacing the original promoter. Dr. __XXX__’s research results indicated the rpt1 sequence play roles as enhancer and promoter in mycobacterial gene expression in vivo. Dr. __XXX__’s work provided new understanding of a novel mycobacterial gene regulatory element and has been reported at several international meetings.
The expression system generated by Dr. __XXX__ also showed positive results when introduced into BCG system. BCG is the only vaccine for tuberculosis and the safest vaccine for human being. The modification of BCG using recombinant DNA technology aimed to improve the efficacy of tuberculosis vaccination and even exploited it to treat or prevent other diseases, such as tumor immunotherapy. Dr. __XXX__’s system has very practical value to immune patients with prostate cancer with human prostate cancer marker that could prevent the metastasis of micro-follicle of tumor cells after surgical removal of the original tumor. Therefore, NYMC patented Dr. __XXX__’s work.
Another interesting part of Dr. __XXX__’s work is to recognize the interaction of mycobacterial DNA with host proteins. Dr. __XXX__ demonstrated that rpt1 has specific binding with human nuclear protein lysate from U937, A549, and HeLa cell lines. The proteins purified using pull-down experiment from different cell lines share a common protein, Ku70. Ku70 is a subunit of DNA-dependent protein kinase (DNA-PK). rpt1 also showed specific activation of DNA-PK in low dosage. Since DNA-PK has shown to link the activation of NF-kB pathway with the endocytosis of bacterial DNA, rpt1, as a mycobacterial DNA element, could interact with host cells by affecting the activity of host DNA-PK.
Dr. __XXX__ was the primary researcher to creatively develop all above knowledge of mycobacterial pathogenesis using his vast expertise and perseverance. His work is thus of obvious and crucial significance to the US healthcare and economy and to improvement of disease management in patients. Dr. __XXX__ is an innovative, imaginative, independent scientist who brings the highest levels of integrity and excellence to his research work. He is only interested in the most advanced and highest goals of biomedical research and he pursues his goals with utmost dedication, passion and critical assessment. The research community of this country will benefit for years to come from scientist as the caliber of Dr. __XXX__.” (See Exhibit 33)
Exhibit 33: Testimonial letter from Dr. XXX XXXl, Professor and Vice–chair for Researcg, Department of Medicine, XXX Center for BioDefense at New Jersey Medical School, NJMS-National Tuberculosis Center of Medicine and Dentistry of New Jersey (UMDNJ) (UMDNJ)
（to be continued）
