CURRICULUM VITAE

University of Pittsburgh

School of Medicine

BIOGRAPHICAL

Name:  Lingzhi Cai, M.D., Ph.D.  Birth Date: 08/12/1960

Home Address:  7929 Riverview Ave Birth Place:  Jilin, China

Pittsburgh, PA 15218

Home Phone:  412-760-4376 Citizenship:  P. R China.

Business Address: University of Pittsburgh E-Mail Address:  lic27@pitt.edu

Division of Endocrinology

200 Lothrop Street

E1140 Thomas E. Starzl Biomedical Science Tower

Pittsburgh, PA 15213-2536

Business Phone: (412) 648-2273 Business Fax: (412) 648-3290

 

EDUCATION and TRAINING

GRADUATE:

Dates Name and Location of Institution Degree (Year) Major Subject

1983 Norman Bethune Medical University M.D. (1983) Medicine

 Chang Chun, China

1999 Department of Core Laboratory Masters Medicine

 Norman Bethune Medical University 

 Chang Chun, China

 

2004 Department of Pediatrics Ph.D. Pediatrics

Nippon Medical School Hospital

Tokyo, Japan

 

APPOINTMENTS and POSITIONS

Years Name and Location Rank/Title

1983-1989 Nursing College of Jilin University, Chang Chun, China Medical Educator

1989-1992 Department of Pediatrics Physician in Pediatrics

 China-Japan Union Hospital (now Jilin University) (Clinical, Teaching, & Research)

 Norman Bethune University, Chang Chun, China

 

1993-1996 Department of Pediatrics Physician in Pediatrics

 China-Japan Union Hospital (now Jilin University) (Clinical, Teaching, & Research)

 Norman Bethune University, Chang Chun, China

 

1996-1999 Department of Core Laboratory Masters Candidate in Medicine

 Norman Bethune Medical University, Chang Chun, China

 

1999-2000 Shenzhen Children Hospital Attending Physician in Pediatrics

 Shenzhen 51800, Guangdong, China (Clinical, Teaching, & Research)

 

2000-2004 Department of Pediatrics Ph.D. Candidate in Pediatrics

Nippon Medical School Hospital, Tokyo, Japan

 

2005-2008 Department of Neurology Postdoctoral Research Associate

University of Pittsburgh, Pittsburgh, PA USA

 

2008-2009 Division of Endocrinology, Department of Medicine Postdoctoral Fellow

University of Pittsburgh, Pittsburgh, PA USA

 

2009-present Division of Endocrinology, Department of Medicine Research Assistant

University of Pittsburgh, Pittsburgh, PA USA

 

MEMBERSHIPS in PROFESSIONAL and SCIENTIFIC SOCIETIES

Organization  Year

American Society of Gene and Cell therapy (ASGCT)  2008, 2012

American Society of Biochemistry and Molecular Biology (ASBMB) 2012

 

HONORS

Title of Award  Year

Medical Fellowship for Outstanding Researcher in Japan 1992-1993

Medical Health Care Foundation, Chinese Ministry of Health, & China-Japan Medical Association and Sasagawa

 

Medical Fellowship for Outstanding Researcher in Japan 2000-2001

Medical Health Care Foundation, Chinese Ministry of Health, & China-Japan Medical Association and Sasagawa

 

Outstanding Presenter Award

International Communication Center, Nippon Medical School, Japan 2000

 

PUBLICATIONS

Refereed published manuscripts

  • Cai L, Zhao S. Serum soluble IL-2R and its clinical value in children with acute thrombocytopenia. Chinese Journal of Hematology. 1996;17:151-152.
  • Zhao S, Cai L, Wang X. The level of anti-GPM antibody in the blood circulation in children with non-GPS nephrosis. Journal of Chinese Immunology. 1997;13:378-380.
  • Cai L, Zhao S, Kou C. Serum soluble IL-2R and its clinical value in children with recurrent respiratory infections J N Bethune Univ Med Sci. 1998;24(5):487-488.
  • Cai L, Wang W. Measurement of reactive oxygen species in neutrophils by flow cytometric analysis. J N Bethune Univ Med Sci. 1998;24(5): 556-558.
  • Wang Y, Cai L, Guan J, Chen F. Reactive Arthritis (Reiter’s Syndrome). J N Bethune Univ Med Sci. 1998;24 (6): 646.
  • Cai L, Cui Y, Wang W, Lju R, Shao H, Cai W. Fluorescent intensity of reactive oxygen species of neutrophils in peripheral blood circulation and its clinical value in children with acute infectious diseases J N Bethune Univ Med Sci. 1999;25(2):152-153.
  • Cai L, Gao S, Zhao S, Zhang L, Wang W. The value of reactive oxygen species in leukocytes for distinguishing between bacteria and viral infections. Journal of Clinical Pediatrics. 1999;17(5):304-306.
  • Cai L, Gao S, Yang Y, Zheng D, Wang W, Ahang G, Fuyong Q. Study on the relationship between apoptosis and reactive oxygen species of cancer cell lines induced by anti-carcinogens. Chinese Journal of Hematology. 2001;22(5): 249-251.
  • Asano T, Uchikoba Y, Cai L, Kawahigashi K, Maeda M, Shimizu L, and Fukunaga Y. Acute Suppurative Thyroiditis in 7 Year-old girl with Piriform Sinus Fistula. J Nippon Med Sch. 2002;69(6):593-596.
  • Asano T, Matsumoto T, Cai L, Maeda M, Uchida E, Tajiri T, and Fukunaga Y. Solid and cystic tumor of the pancreas in a 12-Year-old boy. Pediatr Int. 2003;45(3):339-341.
  • Orimoto M, Maeda M, Cai L, Hayakawa J, Ueda T, Migita M, and Asano T. Successful immunosuppressive therapy for a child with myelodysplastic syndrome. Med and Pediatr Oncol. 2003;40(5):334-335.
  • Migita M, Shimada T, Hayakawa J, Cai L, Morita T, Ohshiro K, Fukunaga Y. Home treatment with enzyme replacement therapy in a 5-year-old girl with type 2 Gaucher disease. Pediatr Int. 2003;45(3):363-365.
  • Asano A, Cai L, Hayakawa J, Fukunaga Y. Analysis of resistance-related gene expression in doxorubicin resistant leukemia cell line by DNA microarray. Japanese J of Pediatr Hematology. 2003;17(5):340-345.
  • Cai L, Migita M, Hayakawa J, Fukunaga Y. Establishment of modified retroviral vector targeting X-linked severe combined Immunodeficiency. J Nippon Med Sch. 2004;71(1):51-56.
  • Reay DP, Bilbao R, Koppanati BM, Cai L, O’ Day TL, Jiang Z, Zheng H, Watchko JF, and Clemens PR. Full-length dystrophin gene transfer to the mdx mouse in utero. Gene Ther. 2008;15(7):531-6.
  • Kienesberger PC, Lee D, Pulinilkunnil T, Brenner DS, Cai L, Magnes C, Koefeler HC, Streith IE, Rechberger GN, Haemmerle G, Flier JS, Zechner R, Kim YB, and Kershaw EE. Adipose triglyceride lipase deficiency causes tissue-specific changes in insulin signaling. J Biol Chem. 2009;284(44):30218-29. PMCID: PMC2781577.
  • Basantani MK, Sitnick MT, Cai L, Brenner DS, Gardner NP, Li JZ, Schoiswohl G, Yang K, Kumari M, Gross RW, Zechner R, Kershaw EE. Pnpla3/Adiponutrin deficiency in mice does not contribute to fatty liver disease or metabolic syndrome. J Lipid Res. 2011;52(2):318-29. PMCID: PMC3023552.

Manscripts submitted or in preparation

  • Yang Z, Hulver M, McMillan RP, Cai L, Kershaw EE, Yu L, Xue B, and Shi H. Regulation of Leptin and Insulin Signaling by Muscle Suppressor of Cytokine Signaling 3 (SOCS3). J Biol Chem. 2011. Submitted for publication.
  • Basantani BK,*, Sitnick MT*, Cai L*, Schoiswohl G, Yazbeck CF, Distefano G, Schreiber R, Kienesberger PC, Bickel PE, Liu J, Zechner R, Ritov V, Delany JP, Coen P, Goodpaster BH, and Kershaw EE. Transgenic overexpression of ATGL/Pnpla2 in murine skeletal muscle reduces intramycellular triacylglycerol content but does not influence systemic glucose or lipid metabolism. In preparation. * Authors contributed equally to this work.

Published abstracts (not yet published in full form)

  • Cai L, Carmen Bertoni, Thomas A Rando and Paula R. Clemens. Oligodeoxynucleotide-mediated gene correction of the dystrophin gene in utero. American Society of Gene Therapy 11th Annual Meeting 2008. Abstract Number: 450950.

Published books or books in preparation

  • A chapter for a Methods in Molecular Biology book on Gene Correction (published Humana Press/Springer Protocols)

PROFESSIONAL ACTIVITIES

TEACHING:

  • Year(s) taught: 1983 - 1989
  • Institution: Nursing College of Jilin University, Chang Chun, China
  • Name of course: Pediatrics and Japanese language
  • Description of teaching role: Lecturer
  • Type of students and average number each year: 80-100 first year nurses each year
  • Contact time: 100 hours per year
  • Year(s) taught: 1989 - 1990
    Institution: University of Chang Chun School of Medicine, Chang Chun, China
  • Name of course: Pediatrics and Japanese Language
  • Description of teaching role: Lecturer
  • Type of students and average number each year: 50-60 physicians per year
  • Contact time: 50 hours per year
  • Year(s) taught: 1990 - 1991
    Institution: China-Japan Union Hospital, Norman Bethune University (Presently Jilin University), Chang Chun, China.
  • Name of course: Pediatrics in Japanese Language
  • Description of teaching role: Lecturer
  • Type of students and average number each year: 50 first year medical students (Japanese language class) per year
  • Contact time: 32 hours per year
  • Year(s) taught: 2001, 2002
    Institution: Nippon Medical School Hospital, Tokyo, Japan. 
  • Name of course: Molecular Biology: (1) DNA extraction and Southern blot analysis. (2) RNA extraction and Northern blot analysis
  • Description of teaching role: Lab Instructor
  • Type of students and average number each year: 80-100 second year medical students per year
  • Contact time: 16 hours per year
  • Advisory and supervisory responsibilities in clinical or laboratory setting:
  • Year(s) performed: 1983 – 1989
    Description of responsibilities: Clinical Attending/Teaching Pediatrician in Pediatrics at First Hospital, Norman Bethune University, Chang Chun, China Teaching     responsibilities included supervision and training of 80 to 100 nursing students in clinical setting.
  • Year(s) performed: 1989 – 1992 and 1993 - 1996
    Description of responsibilities: Clinical Attending/Teaching Pediatrician     in Pediatrics at China-Japan Union Hospital, Norman Bethune University, Chang Chun, China Teaching responsibilities included instruction and supervision of 50 to 60 medical students and physicians per year in the outpatient and inpatient clinical setting for twelve months per year    .
  • Year(s) performed: 2008 – present
    De    scription of responsibilities: Laboratory supervisor     in Endocrinology, Diabetes, and Metabolism at University of Pittsburgh, Pittsburgh, PA. Teaching responsibilities include supervision of undergraduate/graduate students, medical fellows, and/or postdoctoral fellows in the laboratory setting. Supervision includes instruction in laboratory techniques and scientific methods as well as laboratory and institutional protocols.
  • Estimate of hours per year: 5-10 hours per week per trainee for 1-3 trainees per year

RESEARCH:

1. Grant support

Current Grant Support :

 Grant # Grant Title (PI) Years Source

1R01DK090166 “Contribution of ATGL to lipotoxicity  Kershaw 2011-2016 NIH

and the metabolic syndrome”

HHMI Early “Contribution of PNPLA proteins to Kershaw 2009-2014 HHMI

Career Award lipotoxicity and the metabolic syndrome”

 Junior Scholar “Contribution of adiponutrin/Pnpla3  Kershaw 2010-2012 Univ Pittsburgh

 Award to the metabolic syndrome”

2. Seminars and invited lectureships related to your clinical and/or research interests

Research Seminars and invited presentations

Date Title Location

Nov 2000 “Establishment of Modified Retroviral Vector Nippon Medical School, International

Targeting X-Linked Severe Combined Communication Center

“Immunodeficiency”

 

Aug 2008 “Oligodeoxynucleotide-mediated gene  American Society of Gene Therapy

correction of the dystrophin gene in utero International Conference

3. Other research related activities.

Peer review

Year Role Name of Journal

2000- Ad hoc reviewer Chinese Medical Association Professional Journal, Chinese Journal of Cancer

4. Detailed description of past and current research

Research Scientist / Masters Candidate 1990-2000

Department of Pediatrics, China-Japan Union Hospital (now Jilin University), Norman Bethune

University, Chang Chun, China

As a pediatrician and pediatric research scientist, my research focused on the diagnostic and therapeutic utility of measuring reactive oxygen species (ROS) in peripheral blood leukocytes in children with hematologic and infectious diseases. I demonstrated that measurement of ROS production in peripheral leukocytes was clinically useful for differentiating bacterial and viral infections (and hence the need for antibiotics) in children with acute infections. I then extended my studies of ROS to determine their contribution to programmed cell death (apoptosis) induced by chemotherapeutic agents in hematological malignancies. I determined that several commonly used anti-cancer drugs such as etoposide (VP16), cisplatin (DDP), and adriamycin (ADR) induce apoptosis in human erythromyeloblastoid leukemia (K562) tumor cell lines by increasing production of ROS. These studies were critical in defining key mechanisms of drug sensitivity and resistance in the treatment of hematological malignancies. The above work resulted in four first author publication. As a result of this work, I developed special skills related to the quantification of ROS using fluorometric methods.

Publications resulting from this work:

    • Cai L, Wang W. Measurement of reactive oxygen species in neutrophils by flow cytometric analysis. J N Bethune Univ Med Sci. 1998;24(5): 556-558.
    • Cai L, Cui Y, Wang W, Lju R, Shao H, Cai W. Fluorescent intensity of reactive oxygen species of neutrophils in peripheral blood circulation and its clinical value in children with acute infectious diseases J N Bethune Univ Med Sci. 1999;25(2):152-153.
    • Cai L, Gao S, Zhao S, Zhang L, Wang W. The value of reactive oxygen species in leukocytes for distinguishing between bacteria and viral infections. Journal of Clinical Pediatrics. 1999;17(5):304-306.
    • Cai L, Gao S, Yang Y, Zheng D, Wang W, Ahang G, Fuyong Q. Study on the relationship between apoptosis and reactive oxygen species of cancer cell lines induced by anti-carcinogens. Chinese Journal of Hematology. 2001;22(5): 249-251.

Research Scientist / PhD Candidate 2000-2004

Department of Pediatrics, Nippon Medical School Hospital, Tokyo, Japan.

Based on research excellence during my Masters work, I was awarded a prestigious medical research fellowship (awarded jointly by the Medical Health Care Foundation, Chinese Ministry of Health, & China-Japan Medical Association, and Sasagawa) to continue my research training at Nippon Medical School in Japan. My research had two major focuses:

1) Defining mechanisms of chemotherapeutic drug sensitivity/resistance. As a logical extension of my prior work, I continued to identify mechanisms that contribute to the effectiveness of chemotherapeutic agents in hematological malignancies. To do so, I established human erythromyeloblastoid leukemia (K562) tumor cell lines that were either sensitive (K562-P) or resistant (K562-ADM) to the chemotherapeutic agent doxorubicin (as well as other agents). I then used microarray technology to identify several candidate genes/pathways contributing to drug sensitivity/resistance. These studies were critical in developing effective strategies to improve the effectiveness of chemotherapy for hematologic and other malignancies. This work resulted in one co-author publication. As a result of this work, I developed expertise in DNA microarray technology.

2) Identifying improved methods for gene therapy of hematological disorders. The second focus of my research was to develop a gene therapy strategy for X-linked severe combined immunodeficiency syndrome (X-SCID), a devastating immunodeficiency disorder resulting from an abnormal Xq13.1 gene on the X-chromosome that is responsible for the functionality of the interleukin 2 receptor (IL2R). Existing gene therapy strategies using moloney murine leukemia virus (MoMLV)-based vector systems were limited by insufficient maintenance of therapeutic gene expression. To overcome this problem, I generated a novel therapeutic vector (modified MND vector). I then used this improved viral vector to generate an MND-IL2R gene therapy system for X-SCID and tested its effectiveness in human CD34+ hematopoietic progenitor cells. These studies provided an improved viral delivery system for gene therapy of X-SCID as well as other disorders. This work resulted in one first author publication. As a result of this work, I gained highly specialized skills related to gene therapy.

Publications resulting from this work:

    • Asano A, Cai L, Hayakawa J, Fukunaga Y. Analysis of resistance-related gene expression in doxorubicin resistant leukemia cell line by DNA microarray. Japanese J of Pediatr Hematology. 2003;17(5):340-345.
    • Cai L, Migita M, Hayakawa J, Fukunaga Y. Establishment of modified retroviral vector targeting X-linked severe combined Immunodeficiency. J Nippon Med Sch. 2004;71(1):51-56.

Research scientist / Postdoctoral Associate 2005-2008

Department Neurology, University of Pittsburgh, Pittsburgh, PA USA

As a result of my special expertise in gene therapy, I was recruited by Dr. Paula Clemens to join the Department of Neurology at the University of Pittsburgh. My research focused on developing pre-clinical in utero gene therapy strategies targeting Duchenne Muscular Dystrophy (DMD), a severe and debilitating form of muscular dystrophy resulting from mutation in the dystrophin (Mdx) gene. These studies extended my prior work by applying gene therapy strategies in utero. I generated and tested gene therapy systems for delivery of a functional Mdx gene to fetal skeletal muscle of dystrophin-deficient (Mdx-KO) mice in utero, with the goal of correcting the genetic defect in muscle progenitor cells. I then performed extensive phenotypic and molecular analysis to assess the effectiveness of gene correction. These studies demonstrated the feasibility of in utero gene therapy strategies and provided support for this approach in the treatment DMD. This work resulted in one co-author publication as well as an abstract at the Annual Meeting of the American Society of Gene Therapy (2008). As a result of this work, I further developed my expertise in gene therapy. I also developed specialized skill in the imaging analysis of skeletal muscle.

  • Publications resulting from this work:
    • Reay DP, Bilbao R, Koppanati BM, Cai L, O’ Day TL, Jiang Z, Zheng H, Watchko JF, and Clemens PR. Full-length dystrophin gene transfer to the mdx mouse in utero. Gene Ther. 2008;15(7):531-6.

Research scientist/ Postdoctoral Associate 2008-present

Division of Endocrinology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA

As a result my special research skills related to imaging and evaluation of skeletal muscle, I was recruited by Dr. Erin Kershaw to the Division of Division of Endocrinology. My primary research focus has been to develop highly sophisticated imaging techniques to simultaneously visualize and accurately quantify intracellular lipids and proteins associated with lipid metabolism in murine skeletal muscle, a process that is extremely difficult in this animal model system. I have successfully developed these techniques in murine muscle as well as several other murine tissues. I have subsequently applied these techniques to multiple genetically-engineered murine models of abnormal lipid metabolism. This contribution as well as other contributions has already resulted in two published co-author manuscript and submission of another collaborative co-authored manuscript. As a logical progression of my earlier work related to muscular dystrophy, I am working to better understand the contribution of novel lipid metabolizing enzymes to lipid-associated myopathies as well as to metabolic disease. I have developed animal models with skeletal muscle-specific targeted deletion and transgenic overexpression of the rate-limiting enzyme in triacylglycerol hydrolysis. I am currently assessing these models for alterations in systemic/tissue-specific metabolism as well as muscle function. Two manuscripts related to this work are currently in preparation. More recently I have made a novel and exciting discovery linking lipid metabolism to carcinogenesis and immune system dysfunction. These potentially high impact discoveries link my current and prior experience/expertise and will be the focus of my future work. In this experience, I have developed special skills related to the simultaneous quantitative imaging of intracellular lipids and proteins using highly sophisticated imaging techniques and have also further developed my expertise in metabolically and functionally characterizing genetically-engineered murine models.

  • Publications resulting from this work:
  • Kienesberger PC, Lee D, Pulinilkunnil T, Brenner DS, Cai L, Magnes C, Koefeler HC, Streith IE, Rechberger GN, Haemmerle G, Flier JS, Zechner R, Kim YB, and Kershaw EE. Adipose triglyceride lipase deficiency causes tissue-specific changes in insulin signaling. J Biol Chem. 2009;284(44):30218-29. PMCID: PMC2781577.
  • Basantani MK, Sitnick MT, Cai L, Brenner DS, Gardner NP, Li JZ, Schoiswohl G, Yang K, Kumari M, Gross RW, Zechner R, Kershaw EE. Pnpla3/Adiponutrin deficiency in mice does not contribute to fatty liver disease or metabolic syndrome. J Lipid Res. 2011;52(2):318-29. PMCID: PMC3023552.

5. Special skills

  • Highly specialized skills
    • Special expertise in gene therapy technology including generating delivery systems, delivering therapy in vitro and in vivo (including in utero), and assessing effectiveness of therapy.
    • Special expertise in simultaneous quantitative imaging of intracellular lipids and proteins using of high sophisticated immunohistochemical and immunofluoroesent techniques including use of light, confocal, and electron microscopy and associated imaging software.
    • Special expertise in generating and phenotyping genetically-engineered murine models.
  • Research skills
    • Molecular biology: (a) DNA extraction and Southern blot analysis. (b) RNA extraction and Northern blot analysis. (c) Construction of vectors, gene recombination, and gene cloning. (d) Gene expression, DNA microarray, and FACS analysis. (e) DNA sequencing, PCR, qPCR, etc.
    • Cell culture: Monolayer or suspension, primary or continuous cell lines.
    • Stem cell biology: Isolation of the hematopoietic stem cells (HSCs) from cord blood, propagation and transduction in vitro, and transplantation of transduced HSCs.
    • Proteins and antibody techniques: production of monoclonal antibodies including cell fusion, screening, cloning, and ELISA analysis’ protein purification and Western blot analysis.
    • Molecular Virology: Virus culture, isolation.
    • Serology: Immunofluorescence, immunohistochemistry, and immunoprecipitation.
    • Small animal experiment: Oligonucleotide-mediated gene correction (including in utero) and analysis of gene expression at protein and DNA levels.
    • Experimental design and planning skills.
    • Data analysis and problem-solving skills.
    • Informational technology and research presenting
  • Teaching
    • Experience teaching in a variety of settings (clinical, laboratory, and classroom)
    • Experience working with students at a variety of levels (beginner to advanced)
    • Effective at preparing and using instructional aids including written and audio-visual material
    • Experience teaching both Chinese and English to non-native speakers
    • Experience fostering an effective learning environment encourages intellectual growth.