I filed my I-140 and I-485 by myself without the help of the lawer on 9/26/2005, no receipt and no check cashed.So I do not know my case is good experience or bad lesson.I got the news of new policy 9/16/2005, only spent about 10 days to prepare supporting letters and petition letter. It's a way to show you are excellent, so I choice to fight the challenge.
My I-140 is the field of biomedical research, healthcare is benefit to US and the benefits are national. The key point is elucidate if asking you to apply LC, it will play the adverse-effet on US.You may say your project is complecated and your experts is competitive,your experience ar ...so on
Good lucks to all.
____________________________________
X, M.D.
X street
X, PA 178xx
Tel.: 570-xxx-xxxx(daytime)
570-xxx-xxxx(evening)
Email: x@yahoo.com
September 25, 2005
US Citizenship and Immigration Services
Vermont Service Center
75 Lower Welden Street
St. Albans, VT 05479-0001
Re: I-140 Immigrant Petition as Alien Worker- A member of the professions holding an advanced degree or an alien of exceptional ability- National Interest Waiver
Petitioner/Beneficiary: X, M.D.
Dear Sir/Madam:
I am filing an I–140 Immigration Petition (concurrent filling I-485) for Alien Worker for myself under the section: A member of the professions holding an advanced degree or an alien of exceptional ability – National Interest Waiver. (Sec.203 (b)(2) ). Your kind help to my case is greatly appreciated.
Educational and research background
From 1979 to 1984, I had received 5 years biomedical training at Department of Medicine, X Medical University at China. I got Bachelor of Medicine in China, which is equivalent to a first professional degree in medicine (M.D.) from an accredited medical school in the United States. From 1988 to 1991, I had received 3 year full time training on research of biochemistry and pathology as well as high level surgery skill at Shanghai, China. I got Master of Medicine in China, which is fully equivalent to an American master’s degree in one of the biomedical sciences. In China, my research focused on biochemical and histological study of hypertrophic scar, expanded tissue and ischemia-reperfusion damage on flap using animal model. I have published 2 peer-reviewed articles reporting my experiment results on some prestigious biomedical magazines in China. Another 3 papers published in China are clinical. My previous research experience and expertise in pathological and histological study prove to be extremely valuable and relevant for my current projects.
Current employer
As a postdoctoral fellow, I have been working at Dr.X’s laboratory of X Center for Research, X Health System at X, Pennsylvania since September 11, 2001 to present through an open competition around world. Dr. XX’s primary research focus is on the molecular mechanism underlying disease X. In particular, the goal of Dr.XX’s lab is to understand the function of a group of transmembrane proteins called sarcolycans, their mutations cause limb-girdle disease X (LGMD). His finding during the past few years have been published in many highly regarded peer-reviewed journals in the US (Muscle & Nerve 29(3):xx-xx; Journal of Clinical Investigation 110(6):xx-xx; Journal of Cell Biology 148(1):xx-xx; Journal of Cell Biology 143(7):xx-xx). Last year, he has also been awarded a three-year grant (#MDAxxxx) totaled $290,000 from the Disease X Association (MDA), one of the largest private non-profit health agencies in the US.
The Sigfried and Janet X Center for Research provides a focus for laboratory research and research training, and supports the clinical staff in their research programs. The X Center, located on the campus of the X Medical Center in X, PA, contains 65,000 square feet of laboratories well equipped with state-of-the-art instrumentation, including core facilities for confocal microscopy, protein mass spectroscopy, gene microarray analysis and DNA sequencing, as well as an AAALAC-accredited animal facility. The primary mission of the X Center is to conduct original and innovative research that contributes new knowledge to biomedical science. X Center scientists investigate a range of topics in cardiovascular biology, cancer, neuromuscular disease and developmental biology, with a focus on molecular and cellular mechanisms. Examples of specific areas of investigation include: mechanisms of hormone signaling; the role of hormones and exercise in heart failure; control of cell division and differentiation of tumor cells; and development and regeneration of the peripheral nervous system. A significant fraction of the research carried out in the X Center is supported by grants from the National Institutes of Health.
A second important function of the X Center for Research is to conduct research training and education. Postdoctoral fellows, residents and clinical fellows receive rigorous training in modern cellular and molecular biological research. The X Center enhances the quality of medical care that is available to the patients served by the X Health System. A major new initiative of the X Center for Research is to develop the Henry Hood Research Program in Human Genetics. This will enable X Center investigators to tap into the pool of data that is being generated by large-scale gene mapping and sequencing projects, such as the Human Genome Project. The Genetics research program will also establish important new areas of clinical research at X, and provide novel insights into the molecular and genetic basis of disease.
Founded in 1915, X Health System provides more than two million people in 38 counties in Pennsylvania a complete continuum of quality health care. The X Health System enjoys national recognition as a model for quality health service delivery and has been listed in Best Hospitals in America, and our physicians have been listed in The Best Doctors in America. X is a physician-led health care system, dedicated to health care, education, research and service.
Disease associated with my research
The disease X are an important group of inherited disorders. They are all characterized by progressive muscle wasting and weakness in which the muscle histology revealed muscle fiber degeneration and necrosis and later invasion by connective tissue and fat. Based on the distribution of muscle involvement coupled with muscle protein and molecular genetic studies over 30 different types are now recognized. Some disorders are severe, begin in early childhood. They may result in a cardiomyopathy or/and mental retardation. Typically, most patients die in their late twenties or early thirties. There is as yet no form of treatment that can arrest the progression of disease X.
Protein Xs (SG) are a group of transmembrane proteins predominantly expressed in muscle. They consist of four subunits (α, β, γ, δ-SG) and are closely associated with dystrophin and other membrane-associated proteins to form a larger complex called dystrophin-associated protein complex (DAPC) on the plasma membrane. Mutations in protein Xs have been reported to cause autosomal-recessive limb-girdle disease X (LGMD) type 2C-F, a group of disease X with characteristics of affecting the large proximal muscles of the arms and legs. Currently, the function of the protein Xs is not completely understood. They are thought to stabilize the DAPC and are important for muscle membrane integrity. However, there is increasing evidence that they are involved in non-structural functions by interacting with other proteins. To investigate the physiopathological mechanism of Limb-girdle Disease X and to develop the treatment, we must figure out the functions of protein Xs.
My projects and achievements
Project 1: Identify protein X-associating and dystrophin-associating proteins using an innovative yeast two-hybrid system (Cyto Trap®, Stratgene)
Most proteins play their roles in one subunit of complex or together with associating proteins. One of methods to explore the functions of proteins is to search their associating proteins.
I cloned extracellulor domain of α, β, γ, δ protein X and C-terminal of dystrophin as baits into pSos vector as bait, co-transfect to yeast cell with mouse skeletal muscle cDNA library on pMyr ventor, this cDNA library presents all genes can be express to proteins (called fishing proteins here) in skeletal muscle. For one yeast cell, only one fishing protein and bait protein can express. Once these two proteins can interact, the yeast cell will survive in 37°C. Extract DNA from the positive yeast cells, check the sequence and do BLAST (search and compare) from the database on the web, finally several candidates (A.B,C,D,E) have been found. A is an unknown protein, which contains two well-characteristic domains: WWE domain mediates some protein-protein interaction in ubiquitin and ADP ribose conjugation systems; poly(ADP-ribose) polymerase catalytic domain plays the role in ADP–ribosylation activities, modifying the proteins to participate in various signaling pathway. Using heterogenous expressing system this interaction between A and b-SG has been confirmed in co-immunoprecipition experiment. Extension study is in process. I want to add all the work above is done independently myself.
Project 2: Structure analysis of protein X.
Another way to study the functions of proteins is to investigate the structure first.
Using limited proteolysis, co-immunoprecipitation and mutagenesis, I have shown that the extracellular region of protein Xs is divided into two functional domains separated by a flexible hinge region. The N-terminal half domain is invlolved in protein X interaction whereas the C-terminal half domain is critical for plasma membrane localization. Mutation studies revealed a number of structural features in protein Xs that are important for protein X assembly and targeting to the cell surface. According my data, β-SG, γ-SG and δ-SG are closely associated with each other but spatially apart from α-SG. The tri-meric β/δ/γ–SG complex is though to organize in a highly symmetrical manner on the cell surface. This overall arrangement could result in a specific conformation that allows protein Xs to interact with a yet unidentified protein in the extracellular matrix. My results in this new and important field lead to better understanding of protein Xs structure and the molecular mechanism underlying LGMD. My findings have been submitted to Human Molecular Genetics, a prestige peer-reviewed professional journal in biochemical research and the manuscript is currently under review, with the title: “Identification of Functional Domains in Protein Xs Essential for Their Interaction and Plasma Membrane Targeting”. I am the first author in the paper.
This project is funded by the Disease X Association (MDA) (#MDAXXXX), one of the largest private non-profit health agencies in the US. I am crucial investigator in this project.
Project 3: Identification of novel protein X-interacting proteins.
Using bioinformatics searching, X subunit (X) of the vacuolar ATPase was listed as a potential candidate that associates with δ-SG protein in low level insect, Drosophila. To confirm the interaction between δ-SG and X in mouse and human, DNA construct encoding V5-tagged X was co-transfected with each protein X in COS-1 cells. In co-immunopricipitation experiments, X was specifically associated with δ-SG or the highly homologous γ-SG but not with α-SG or β-SG. RT-PCR confirmed the expression of X transcripts in skeletal muscle and C2C12 myotubes.
To support their association in vivo, protein Xs were shown to co-immunoprecipitate with X in C2C12 myotubes. Immunostaining of human skeletal muscle fiber with anti-X antibody indicated that X is present in the cytoplasm and co-localized with protein Xs on the muscle membrane.
In the BIO 14.6 hamster, a hamster with genetic defect of δ-SG, iimmunofluorescent staining of X in skeletal muscle revealed clear sign of accumulations on the sarcolemma, suggesting that the distribution of X in muscle is altered in response to the loss of protein Xs.
To identify the domains required for their interaction, I have generated a series of deletion mutations in X and protein Xs and tested for their interaction by co-transfection in COS-1 cells. I found the fourth transmembrane domain of X is required for its interaction with δ-SG.
These are the most important findings in my research projects, I’d like to use part of my supervisor, Dr.X’s supporting letter as a brief lay summary here:
“Using an innovative screening system called Cyro-Trap as well as bioinformatics, Dr. X has identified several candidate proteins that interact with protein Xs. One of them is a subunit of proteinX, an enzyme essential for regulating pH gradient inside the cells.”
“I would like to emphasize that Dr. X is the first person to report this interaction. During the past years, he has done pioneered work in this area and provided compelling evidence that vacuolar ATPase interacts with protein Xs. Recently, Dr. X has used animal models to demonstrate the physiological significance of vacuolar ATPase in disease X. These exciting results provide an entirely new approach to study muscle diseases and offer new opportunities for development of potential drugs and therapies for disease X in the future. Dr. X’s ongoing project is to explore the possibility of using vacuolar ATPase as a therapeutic agent in disease X. In this summer, he has submitted a development grant application to Disease X Association. Meanwhile, a manuscript based on his results is in preparation and will be submitted his results at major national conferences, such as American Society for Cell Biology and the American and American Society of Human Genetics.”
Project 4: Mutation screening of protein Xs in disease X patients:
My work is also involved in the immunohistochemical analysis of muscle biopsies sent to our laboratory from other hospitals. Currently, I have collaborations with many neurologists around the world (Medical School of X University, University of X, X College of Medicine, etc). To find new genes involving in disease X, I check many samples using different antibodies followed by mutation analysis, the preliminary results suggested X deficiency in one patient. Mutation screening of X gene is currently in process.
Future research plan
1). Further characterize the interaction between protein X and X, determine the domain in δ-SG required for interacting with X.
2). Explore the physiological significance of X-X interaction in muscle by overexpression of mutants and RNAi approach.
3). Investigate whether X can promote the assembly and targeting of protein Xs to the plasma membrane.
Research Expertise
1). Molecular biology – DNA cloning and purification, PCR, gel electrophoresis, site-directed mutagenesis, DNA sequencing.
2). Protein chemistry – heterologous expression by mammalian cells, in vitro protein expression, protein gel electrophoresis and Western blots, co-immunoprecipitation, membrane preparation by differential centrifugation, protein purification by lectin chromatography.
3). Protein-protein interaction – yeast two-hybrid system (CytoTrap), cDNA libraries screening.
4). Cell biology – cell culture, DNA transfection, cell surface biotinylation and chemical cross-linking, indirect immunofluorescent and confocal laser microscopy.
5). Pathology – immunohistochemical analysis of muscle biopsy.
6). Surgery – animal surgery and microsurgery technique, tissue transplantation.
7). Bioinformatics – DNA and protein structural analysis, PCR primer design, database searching.
8). Computer – MCSE (Microsoft Certificate System Engineer, 2000)
List of experts providing supporting letters and evaluations
1). Dr. X M. X, Ph. D, Professor of Pediatrics and Genetics of Harvard Medical School, Director of Program in Genomics of Children’s Hospital in Harvard Medical School and Investigator of Howard Hughes Medical Institute. Boston, MA
2). Dr. X A X, M.D, Professor of Pediatrics Vice Chairman for Research in Pediatrics, Children’s Hospital at Hershey Medical Center, XUniversity. Hershey, PA.
3). Dr.X M. X, Ph.D., Staff Scientist, X Center for Research, X Health System. X, PA.
4). Dr. X J. X, Ph.D., Director and Senior Scientist, X Center for Research, X Health System. X, PA.
5). Dr. X Y. X, M.D., Ph.D. Professor of Cellular and Molecular Physiology and of Medicine, Medical School, XUniversity. Hershey, PA, Member of American Society of Clinical Investigation.
6). Dr. X X, Adjunct Professor, Department of Molecular and Cellular Biology, University of X, X, Canada..
a. My work is outstanding:
Dr. X M X, Ph.D.: “In summary, the achievements of Dr. X prove he is a promising scientist, His contributions to the study of the field of disease X are crucial and significant”.
Dr. X J. X, Ph.D.: “ Dr. X’s outstanding productivity and significant contributions in the research area of disease X, which substantially exceed the level normally expected of qualified members of our profession.”
Dr. X A X, M.D.: “Dr. X is an excellent scientist who has made significant contributions to the field of the molecular mechanism underlying disease X (MD).”; “Dr. X’s outstanding performance has shown he is an extraordinary researcher in the field of disease X.”
Dr. X, Ph.D.: “Dr. X is an outstanding scientist who has made significant impacts and discoveries in the field of disease X”; “In summary, Dr. X’s outstanding accomplishments have far-reaching scientific and social impact on US healthcare”; “Dr. X ranks very high among his peers in terms of his experience and comprehensive understanding of muscle physiology and pathology.”
Dr. X X, Ph.D.: “Dr. X is an outstanding researcher who has made many significant contributions to the field of disease X and the involvement of X in this disease”.
Dr. X Y. X, M.D., Ph.D.: “Dr. X is an outstanding scientist who has made original and significant contributions to the field of the molecular biological research of disease X”; “He is an excellent researcher in the field of disease X.”
b. My work has intrinsic merit to the National Interests of the U.S. and my contribution is national:
Dr. X M X, Ph.D.: “Disease X research is really important, with disease X affecting 1 in 3,500 newborn males in this country. With some types of MD, like DuXne Disease X (DMD), survival is rare beyond the early 30s and treatments are not available. ”; “I have no doubt that his research field is clearly corroborating with the national interest of the United States. Awarding him a permanent residency status, I believe, will substantially benefit the national interest of the United States since his research will most likely benefit the United States’ efforts in its fight against disease X. ”
Dr. X J. X, Ph.D.: ” I truly believe taking advantage of Dr.X’s established expertise will benefit the American people.”
Dr. X A X, M.D.: “His research results and his future work are likely to make significant contributions (to) health care in the United Stated, particularly in the fight against disease X disease.”
Dr. X, Ph.D.: “These exciting results provide an entirely new approach to study muscle diseases and offer new opportunities for development of potential drugs and therapies for disease X in the future.”; “I have no doubt that his research is clearly corroborating with the national interest of the US. In my opinion, in order to improve our national healthcare and to maintain our leading role in international medical research, the US must utilize the rare and exceptional talents of scientists like, Dr. X.”; “His research will clearly benefit this country by advancing our knowledge in muscle biology and our efforts in fight against muscle disorders.”
Dr. X X, Ph.D.: “Dr. X’s outstanding research results and many innovative research techniques provide a substantial benefit to the United States. His continued investigations have the potential to contribute directly to healthcare.”
Dr. X Y. X, M.D., Ph.D.: “His research result makes and his future work will make significant contribution to the US healthcare system.”
c. Labor Certification will have an adverse effect on the National Interest of the U.S.
Dr. X Y. X, M.D., Ph.D.: “If Dr. X is required to obtain labor certification from the US Department of Labor, it will disrupt his ongoing research.”
Dr. X J. X, Ph.D.: “If Dr. X is required to obtain labor certification from the US Department of Labor, it will postpone the project he is doing, and bring adverse effects on the national interest of the United States.”
Dr. X X, Ph.D.: “Granting him a permanent residency status, will allow him to contribute directly in the fight against disease X.”
Dr. X, Ph.D.: “Granting permanent residency to Dr. X therefore would be in the best national interest of the US.”
Dr. X A X, M.D.: “Awarding him permanent residency status is in the national interest of the United States.”
Publications，conferences and seminar
I have two first author publications since working at Dr. X’s lab from 2001, one is submitted to Human Molecular Genetics, a prestigious and international leading peer-reviewed professional journal in biochemical research. The manuscript is currently under review. The other is in preparation. I have two experimental papers about biochemistry study in China, another 3 papers are clinical.
I have presented my studying results at major national conferences, such as 44th annual meeting of American Society for Cell Biology at Washington DC last December and 54th annual meeting of the American Society of Human Genetics at Toronto, Canada last October. I will post my new progress in my project December this year at San Francisco at 45th annual meeting of the American Society for Cell Biology.
I also present a seminar to introduce my promising progress to my colleges at X Center for Research, X Health System at X, Pennsylvania last year.
Here is the list involving this petition.
1. Identification of the XDa subunit of a novel protein X-interacting protein. (in preparation, first author)
2. Identification of functional domains in protein Xs (submitted to Human Molecular Genetics)
3. Expression of
4. Effect of Journal of Chinese Surgery. 31(5); xx.
5. The American Society for Cell Biology Meeting, San Francisco, December 10-14, 2005. Poster:
6. The American Society for Cell Biology Meeting, Washington, DC, December 4-8, 2004. Poster:
7. The American Society of Human Genetics Meeting, Toronto, Ontario, Canada, October 26-30, 2004. Poster:
Grant application
Grant name: Application for Neuromuscular Disease Research Development Grant from Disease X Association (MDA), one of the largest private non-profit health agencies in the US.
Project title: The XD subunit of vacuolar ATPase is a novel protein X-interacting protein in LGMD.
Applicant: X, M.D., X Center for Research
Submission date: July, 2005
Status: finished, review is pending till November 1, 2005
Professional Membership
1). Postdoctoral membership of American Society for Cell Biology, founded in 1960, more than 11,000 members are located throughout the United States and in 50 foreign countries and required Ph.D. or other professional degree (e.g., M.D., D.V.M).
2). Student membership of the New York Academy of Sciences, a independent, nonprofit, membership-based organization since 1817, widely recognized as one of the world's foremost organizers of scientific conferences and symposia.
CONCLUSION
My significant discoveries, substantial contributions and excellent abilities in the field of disease X study, documented by my high quality publications submitted and in preparation, well-known experts’ supporting letters, national conference presentations, professional seminar and grant application, approve I am outstanding and significantly ranking very high among my peers. The impacts of my work to the healthcare in the US are definitely national. My comprehensive understanding of muscle physiology and pathology, more than 4 years’ research experiences in same field, multidisciplinary expertise including molecular biology, protein chemistry, protein-protein interaction, cell biology, pathology and bioinformatics, all of these confirms I am extraordinary and exceptional. The labor certificate process would delay or interrupt me from contribution to the new developing field of research of disease X, which is very critical to the fight against this disease in this country and beneficial to U.S. healthcare. It will definitely have adverse effects upon the national interest. Going through the labor certificate process is an obvious disadvantage for me to compete in the labor market and I will be mixed with many other relatively less qualified applicants, no matter how outstanding I am, how significant my contributions are and how critical I am to the projects of disease X study. My work requires sophisticated skills that the minimum qualified worker will not be able to handle. Without the concentration, I can not be efficient and productive as before.
I respectfully request that your office approves my petition and grants me a national interest waiver to expedite my becoming a permanent resident which will allow me to continue my cutting-edge biomedical research, and will substantially benefit poor kids with disease X and improve our nation’s healthcare, dramatically reduce healthcare cost. These are all in the national interest.
The following documents are provided in support of my petition:
1) Form I-140 with a bank check in the amount of $ 190.00;
2) Form ETA 750 part B (in duplicate);
3) X’s Resume documenting scholarly achievements and experience;
4) Supporting letters
5) Copy of publications, conference posters and semina;;
6) Copy of notarized my diplomas and certificate;
7) Copy of evaluation documentation for foreign degree;
8) Copy of evidence of X’s professional membership;
9) Copy of evidence of grant submission to MDA;
10) Copy of X’s notarized birth certificate;
11) Copy of X’s passport, J-1 visa and I-94;
12) Copy of X’s H1B1 approval notice and I-94;
13) Copy of X’s IAP-66 (F 3752480) issued 08/01/2001 to Exchange Visitor Program at X Health System;
14) Copy of X’s DS-2019 issued 04/02/03 to conform to new form requirements;
15) Copy of offer letters;
16) Instruction of X Health System and X Center for Research
17) Copy of X and wife’s notarized marriage certificate
18) Copy of X’s wife, X’s notarized Birth Certificate
19) Copy of X’s wife, X’s passport, J-2 visa and I-94
20) Copy of X’s wife, X’s F1 visa, I-20 and I-94
21) Copy of X’s son, X’s notarized Birth Certificate
22) Copy of X’s son, X’s passport, J-2 visa and I-94
23) Copy of X’s son, X’s H-4 approval notice and I-94
Thank you for your attention and consideration to my petition.
Sincerely yours,
X, M.D.