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Protein or Cell-Based Vaccine Strategies To Cure Cancer
Charles Gullo, Ph.D
A Science Advisory Board Member Since 2005





Dr. Charles Gullo is a Principal Research Scientist and Assistant Professor at Singapore General Hospital in South East Asia. Duke/NUS Graduate Medical School opened its doors in August of 2007 in Singapore as the county’s second medical school. It was the first school in the region to accept medical students only after they had received a bachelor’s degree, (similar to those in the United States), and one that includes a full year of research during its four year program. It has already risen to distinction as one of the few schools in the world for being a primarily team-based, student-centric, facilitation-led medical instruction program. Dr. Gullo helped develop the Immunology teaching program and has been working with others to further refine the Body and Disease course that’s taken in the first year.


Educational Background


I received my first degree in Biology (BSc) at the University of Mary Washington, a small liberal arts university in Fredericksburg, Virginia. I then received my PhD at the University of Virginia in Microbiology at the Beirne Carter Center for Immunology. My PhD thesis was in the area of T cell viral immunology. I furthered my interest in Immunology with a postdoctoral fellowship at the Beth Israel Deaconess Medical Center at the Harvard Medical School complex in Boston, where I specialized in molecular immunology and T cell signaling. My work then focused on T cell SAP and SLAM proteins (signaling molecules involved in T cell differentiation and activation). For seven years I have run a translational science laboratory at SGH, Singapore’s largest hospital. There, I focused my research on cancer immunology, primarily in the areas of cellular vaccine development for B cell cancers, trained students, wrote grants, and published a number of manuscripts.


Professional Background


I initially worked as a medical technologist at Georgetown University Medical Center for several years between my undergraduate and graduate education. There I was involved in prenatal diagnostics in the Biochemical Genetics laboratory in the Dept. of Obstetrics and Gynecology.  I was also involved in some genetic counseling. My first professional position was at the SGH in Singapore where I became the head of the cancer immunology laboratory after working as a senior scientist at a similar lab that focused on multiple myeloma. During my tenure at SGH, I became an adjunct faculty member at the National University of Singapore in the Microbiology Department and the Immunology Program.  I later also became a regular rank assistant professor at the new Duke/NUS GMS where I currently work teaching immunology and assisting other courses in the facilitative process.


Academic and Professional Interests


Over the last seven or so years, I have worn several hats.  The first was a traditional scientist hat, where I was running a laboratory that was focused on making discoveries and publishing those findings. The second was as a trainer role, where I have mentored and trained over 20 students of various backgrounds and levels; from Polytechnic trainees to Medical Doctors. The third and most recent hat has been a medical education teaching role, as assistant professor for the newly developed medical school in Singapore. There, I focused on helping to build the immunology program, facilitate various clinical and researched based sessions, and sit on the curriculum committee, as well as many other critical tasks. Administratively, I currently sit on research grant committees, curriculum committees, thesis committees, and on student admissions committees.



My earliest research interest was in non classical T cell activation such as CD4+ T cells that lyse other cells, (a controversial finding that others have subsequently found as well). I was also involved in working on a newly developed knock out mouse and creating a transgenic mouse that either lacked or overexpressed the SAP in T cells.  That work was primarily concerned with defining T cell subsets and trying to gain a better understanding of T cell signaling. My most current research has primarily focused on multiple myeloma and other blood disorders, although I have published in other areas of cancer as well. My focus has been in understanding the immunobiology of B cell cancers and attempting to develop potential vaccines. I am a firm believer that chemotherapies and drug-based approaches to treating cancer, although particularly useful for many cancers, have reached their treatment limits and have too many side effects. Thus, I strongly believe that protein or cell-based vaccine strategies hold the most promise in the future and will add substantial disease free survival benefits in combination with traditional chemotherapeutic treatments.
  


One particular area of interest of mine is the use of Heat Shock Proteins and vaccines in anti cancer strategies and I have spoken extensively on this subject, written a book chapter, a review and a few publications in that area. Another interest of mine is in the use of global genomics expression profiling,(e.g Microarray), to speed up the discovery process of a potential anti-cancer agent. For example, my collaborators and I have discovered a novel tumor necrosis factor family member that seems to selectively kill MM cells while having no adverse effect on non MM B cells. Our biological observations using CD137L fused to the Fc portion of the Ig molecule was investigated at the molecular level using microarray before it was more extensively tested against tumor specific material. This helped us to determine the molecular mechanisms responsible for the selective anti MM affects in ways that hit-or-miss bench work would have never been able to. We have used this approach to study how certain cytokines might be able to increase the sensitivity of multiple myeloma cells lines to existing drugs like Bortezomib, a potent proteasome inhibitor used in refractory MM, (data not published). My research interests has also covered areas of the potential use of exosomes and umbilical cord dendritic cells in vaccines strategies in addition to novel protein-based and HSP-based vaccines.


Other work that we have published and had interest in is as follows: we have shown that Multiple Myeloma cells have defective CD40/IL-4 functional signaling pathways in comparisons to normal B cells, that MM cells express novel forms of Ku86 (a component of the DNA repair complex) which may lead to the development of a target for immunotherapy, and that UV irradiation may be a sterile and effective method to improve immunotherapy options for MM.


Other Interests


I am an avid traveler and investor. I suppose my second love helps fund my first love. I currently live in South East Asia and that allows me to visit many countries, cities, and islands that I would have never dreamed of doing, while I lived in the United States. Some of my more memorable trips have been to Prague, Melbourne, Bangkok, Pulau Perhentian (Malaysia), and Kuala Lumpur, just to name a few. My goal is to strike off the Philippines and Vietnam from my list of countries to visit. My investment interests span real estate (both land and rental apartments), wine, mutual funds, stocks, options, and others. I always feel like I am still a student even though I have been investing for many years, as there is always so much more to learn!  I also enjoy my morning run as it helps me prepare for my day ahead and of course prevents me from gaining too much weight and keeps me healthy.


Motivations and Aspirations


As a student in high school I was quite average. However, I remember one day taking an advanced biology course with a teacher who was quite inspirational. She encouraged me to consider the area of biology as a potential subject for University. My high school chemistry course certainly reminded me why I did not want to do that subject professionally. After joining university, I really started to enjoy laboratory techniques and the limited experience I had with immunology. However, it was enough for me to decide that I would pursue immunology as a future concentration in graduate school. I did not have a specific inspirational moment where it all clicked. It was a progression of interests that eventually steered me towards a human medical-centric scientific interest. I later realized how much I liked to teach and how much students seemed to enjoy listening to me, thus I grabbed the chance when it came along to participate in medical school education. And although, I was quite nervous with my first few research students, it soon became clear to me that I was born to mentor. I had and still have a passion to provide honest, fun, and rewarding mentor-ship roles for younger scientist.  


Publications:


Gullo C, et. al. Inhibition of Proliferation and Induction of Apoptosis in Multiple Myeloma Cells by CD137 Ligand Signaling.  PLoS One. 2010 May 26;5(5):e10845.



Janil Puthucheary, Doyle Graham, Charles Gullo, Hwang Nian Chih, Lynette Oon1,7, Tan Soo Yong, and Sandy Cook.  Body and Disease 2008: An Integrated Course Teaching Pathology,Pharmacology, Immunology and Microbiology. SGH Proceedings, Vol 18, No. 2, 2009.



Liew PX, Feng G, Gullo C, Teoh G, William YK Hwang.  Use of phage display to isolate specific human monclonal antibody fragments against a potential target for multiple myeloma. Ann Acad Med Singapore. 2009 Jul;38(7):621-9.



Qi Feng, Grace Yee Hui Ho, Charlene Jia Jia Han, Charles Gullo, Ping Law, Steven John Sobak, MBA, William Ying Khee Hwang. Ex Vivo Expansion of Haematopoietic Stem/Progenitor Cells for Pooled Cord Blood Transplantation. SGH Proceedings 2008 Vol. 17 no. 2:73-78.



Gullo C. Low WK and Teoh G.  The association of EBV to Nasopharyngeal Carcinoma (NPC) and the current status on the development of NPC cell lines.  Annals Academy of Medicine, Singapore. 2008; 37 769-777.



Gullo C, Feng G, Cow G, and Teoh G.  Ku86 exists as a full length and natural truncated variant in multiple myeloma cells.  Cancer Cell International, 2008 Apr 29;8(1):4



Gullo C, Hwang W, Poh C, Au M, Cow G and Teoh G Use of Ultraviolet Light Irradiated Multiple Myeloma Cells as Immunogens to generate Tumor Specific Cytolytic T Lymphocytes.  Journal of Immune Based Therapy and Vaccines, 2008 Apr 28;6(1):2.



Gullo C, Poh C, See K, Chua C, Hwang W, and Teoh G.  A Rapid and Sensitive Method of Detecting and Quantifying Hotspot Mutations in the Abelson Tyrosine Kinase Domain of the brc/abl Gene Translocation in Chronic Myeloid Leukemia. Annals Academy of Medicine Singapore Oct. 2006. 35(10); 680-687.



Hwang W*, Gullo C*, Shen J, Poh CK, Tham SC, Cow G, Au M, Chan EWE, and Teoh G.  Decoupling of Normal CD40 / Interleukin-4 Immunoglobulin Heavy Chain Switch Signal Leads to Genomic Instability in RPMI 8226 and SGH-MM5 Multiple Myeloma Cell Line. Leukemia 2006. April 20;(4):715-23. * Co-1st Author



Morra M., Barrington RA, Abadia-Molina AC., Okamoto S., Gullo C., et al.  Defective B cell responses in the absence of SH2D1A. Proc Natl Acad Sci USA 2005 29; 102(13): 4819-23.



Okamoto S, Ji H, Howie D, Clarke K, Gullo C et al.  Expression of the SH2D1A gene is regulated by a combination of transcriptional and post-transcriptional mechanisms.  Eur J Immunol. 2004 Nov; 34(11): 3176-86.



Yong LT., Gullo C., Hwang W., and Teoh G.  The Role of Cytolytic T Lymphocytes in the Eradication of Multiple Myeloma. SGH Proceedings 2004 Vol. 13 no. 2:106-112.



Wang N., Satoskar A., Sweeny R., Howie D., Gullo C. et al. The Cell Surface Receptor SLAM Controls T Cell and Macrophage Functions.  J Exp Med. 2004 May 3; 199(9): 1255-64.



Howie D., Okamoto S., Rietdijk S., Clarke K., Wang N., Gullo C., et al.  The Role of SAP in murine CD150 (SLAM)-mediated T cell proliferation and Interferon gamma production.  Blood 2002 Oct 15;100(8):2899-907.



Wu C., Nguyen K., Pien G., Wang N., Gullo C., et al.  The SAP gene controls T cell responses to virus and terminal differentiation of T helper 2 cells. Nature Immunology 2001 Vol. 2 no. 5:410



Wang N., Morra M., Wu C., Gullo C., et al. CD150 is a member of a family of genes that encode glycoprotiens on the surface of hematopoetic cells.  Immunogenetics 2001 Jul; 53(5): 382



Morra M., Lu J., Poy F., Martin M., Sayos J., Calpe S., Gullo C., et al. Structural basis for the interaction of the free SH2 domain EAT-2 with SLAM receptor on Immunocytes. EMBO 2001 Nov 1(20) 21:5840



Gullo C., Esser M., Fuller T., and Braciale V.  Generation of IL-2 dependent cytolytic T lymphocytes with altered T cell responses derived from antigen-dependent CTL clones. J. Immunology, 1999; 162:6466



Esser M., Krishnamurthy B., Gullo C., et al.  Ca2+ Signaling modulates cytolytic T lymphocyte effector functions. J. Ex. Med 1998; 187:1057



Esser M., Haverstick D., Fuller T., Gullo C., et al.  IL-2 induces Fas ligand/Fas cytotoxicity in CD8+ and CD4+ T lymphocyte clones.  J Immunology, 1997; 158:5612.



Al-Laham M. and Gullo C. Uniparental disomy: A case study in cytogentics.  American Society of Clinical Pathologist Tech sample.  1994; 1:1-4.



Reviews, invited published  papers:
Gullo C, Au M, Feng G and Teoh G. The biology of Ku and its potential oncogenic role in cancer. BBA Cancer Reviews, 2006.  April 1765(2): 223-34.



Gullo C., and Teoh G.  Heat Shock Proteins: to present or not, that is the question. Immunology letters 2004 94(1-2): 1-10.



Books & book chapters:


Gullo C, MaCary P, and Graner M. HSP: Potent Mediators of Inflammation and Immunity, Book Chapter (The role of Heat Shock Proteins in the elicitation of immune responses. A De Maio and A. Asea (eds)).  Springer 2007, vol (1) 173-187.



Invited published abstracts:



Cai Z, Kang Y and Gullo C.  Effects of Soluble CD40L on the expression of TGF-β in Multiple Myeloma Cells.  SGH Proceedings 2006, 15(1): 45-46.



Tan A, Tan WK, and Gullo C.  Developing Sensitive Assays for Measuring the Functional Activation of Multiple Myeloma Cells.  SGH Proceedings 2005, 14(2): 175-6.


Jingwei S, Li L, and Gullo C.  Development of a Sensitive Assay to Detect IL-6 Production in Multiple Myeloma Cell Lines. SGH Proceedings 2005, 14(2): 173-4.





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