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Tuesday, May 25, 2010 1:17:06 PM
Interview with Dr Shi-Jiang Lu
Dr Lu is a senior director at Stem Cell and Regenerative International Inc., and scientific advisor at Advanced Cell Technology Inc., MA, US. He is also adjunct professor at Cha University, Seoul, South Korea. With over 50 scientific publications to his name, Shi-Jiang has authored many key papers in stem cell research, many in collaboration with Dr Robert Lanza. Dr Lu completed his PhD at the University of Toronto, Canada. Here he tells us about his current research interests.
Tell us about the research you are working on at the moment.
My current work focuses on human ES and iPS cell research; specifically human ES and iPS cell differentiation toward specific lineages for clinical applications. Several research directions are currently ongoing in my group:
Donor-less Blood: The shortage of available blood is a constant and critical problem necessitating continual blood drives by agencies such as the Red Cross. We have demonstrated in our scientific paper (Nature Methods, 4:501-509, 2007) that hemangioblasts, a precursor to multiple cell types, can be produced from human embryonic stem cells on a large scale under serum-free conditions. Further, we have been able to show that these hemangioblasts can give rise to both hematopoietic and vascular cell lineages. Importantly, they can be used to create large quantities of erythrocytes (red blood cells), which carry oxygen to tissues throughout the body (Blood, 112:4475-4484, 2008). With our patent-protected technology we are working to produce a donor-less universal blood supply in limitless quantity to treat patients with rare blood types or in emergency situations such as for traumas or on the battlefield.
Donor-less Blood Platelets: Blood platelets are important for clotting and are used to treat a variety of illnesses requiring constant transfusions. Despite this critical need, there is a shortage of available platelets. With our hemangioblast technology we have developed a novel system to efficiently generate megakaryocytes from human embryonic stem cells. Megakaryocytes are bone marrow cells that are responsible for the production of platelets. Other researchers have been able to produce platelets but only by using serum or stromal cells which are animal-derived products. Our megakaryocyte technology produces a safe, reliable source of blood platelets free of animal products.
Dr Shi-Jiang Lu
Donor-less Bone Marrow: Bone marrow is used to treat diseases such as leukemia as well as for cancer patients requiring bone marrow replacement. With our hemangioblast technology we are working to see if transplanted hemangioblasts that we have derived from embryonic stem cells have the capability to grow in a recipient’s bone marrow and produce new bone marrow. Since these cells can be derived in large quantities under serum-free and reproducible conditions, the use of these cells would not be limited by availability, but rather the cells could be grown and differentiated for the precise clinical requirement of the individual with the potential for multiple infusions over the lifetime of the patient if required. For hemangioblasts from human embryonic stem cells, the ability to create banks of cell lines with matched or reduced incompatibility could potentially reduce or eliminate the need for immunosuppressive drugs and/or immunomodulatory protocols altogether. Inasmuch as induced pluripotent stem cell-derived hemangioblasts could be produced from a patient’s own cells, tissue incompatibility could be eliminated completely to avoid a major source of transplantation-related complications.
Retinal Vascular Therapies: Three major eye diseases associated with abnormalities in retinal vasculature (blood circulation in the eye) are glaucoma, diabetic retinopathy, and retinal vein occlusions. All three of these devastating diseases are leading causes of blindness. Glaucoma alone affects over three million people in the United States and about 40% of Americans diagnosed with diabetes have some stage of diabetic retinopathy. We have shown that when hemangioblasts, derived from human embryonic stem cells are injected into the eyes of mice they are capable of repairing damaged retinas and partially restoring vision (Nature Methods, 4:501-509, 2007 and Regenerative Medicine, 4:37-47, 2009). We are working to produce hemangioblasts on a large scale, differentiate them into the cells necessary for eye treatment, and begin a clinical trial to test the efficacy of these cells for the treatment of eye diseases.
Cardiovascular Therapies: Each year, about 1.1 million people in the United States have heart attacks and almost half of them die. We have shown that injection of hemangioblasts, which we have derived from human embryonic stem cells, into mice experiencing induced heart attacks has reduced the mortality rate by 50%. While the mechanism of this success is unknown we suspect it is due to the ability of these hemangioblasts to restore blood flow to areas damaged by heart attack. We are working to study its effectiveness in rats, a more complex model than mice, and thus more similar to humans. The therapeutic potential of this treatment is enormously promising.
Ischemic Vascular Therapies: Ischemia is a condition in which blood flow (and thus oxygen) is restricted to a part of the body. In its most severe form it can cause death. Patients suffering from diabetes can experience ischemia of the limbs requiring amputation. Our studies have demonstrated that injecting hemangioblasts into the ischemic hind limbs of mice has restored the blood flow in those areas to near normal levels. In other studies we have shown that introducing the hemangioblasts into mice wounds results in significantly enhanced healing. We are working to study the effectiveness of this treatment in rats in order to test whether hemangioblasts will be suitable for treatment of ischemia and wounds caused by a number of diseases, such as diabetes.
What was your experience of the OCT4, SOX2, NANOG and LIN28 antibodies and of Proteintech in general?
I tested the four antibodies, all of them are excellent. Most antibodies from Proteintech are excellent and your service is also outstanding. I always recommend my colleagues to Proteintech.
Why did you pursue a career in scientific research?
When I was a college student, to be a scientist was my dream. There was no other career at that time that attracted me the most.
Name one high and one low of your career so far.
Low: Grant reviewer’s comments that “Human ES cell lines are available, why are you using monkey ES cells for this research”: The fact is that the US government has not approved the use of federal funding for human ES cell research. When I resubmitted the proposal including human ES cell lines, the reviewers came back: “You have used monkey ES cells in your research for several years, why do you want to switch to human ES cells”.
High: Half a year after joining Advanced Cell Technology, I discovered and identified hemangioblasts derived from human ES cells.
If you could give just one piece of advice to a young PhD student, what would it be?
Be patient and concentrate on the research you are interested in. Award will come sooner or later.
What do you think will be the most important development in your field in the next decade?
The establishment of safe and authentic human iPS cell lines that are comparable, if not identical, to human ES cell lines. The differentiated derivatives from these safe iPS cells will be used in clinical settings.
What’s your favorite Proteintech antibody?
Anti-human CD31 (PECAM1) antigen antibody.
Who’s your most respected scientist?
Dr Fred Sanger who developed both protein and DNA sequencing.
Western blot or immunofluorescence?
I’ve done a lot of immunofluorescence stains on cells and tissues, sometimes you have to be aware of false positive signals. As for WB, you need a lot of material to start. You also can not tell the location of the protein in a specific cell.
PC or Mac?
I always use PC, no Mac experience.
Monoclonal or polyclonal?
No preference, what I care the most is the specificity.
Science or Nature?
No preference, both are excellent journals.
http://proteintech.wordpress.com/2010/05/25/interview-with-dr-shi-jiang-lu/
Dr Lu is a senior director at Stem Cell and Regenerative International Inc., and scientific advisor at Advanced Cell Technology Inc., MA, US. He is also adjunct professor at Cha University, Seoul, South Korea. With over 50 scientific publications to his name, Shi-Jiang has authored many key papers in stem cell research, many in collaboration with Dr Robert Lanza. Dr Lu completed his PhD at the University of Toronto, Canada. Here he tells us about his current research interests.
Tell us about the research you are working on at the moment.
My current work focuses on human ES and iPS cell research; specifically human ES and iPS cell differentiation toward specific lineages for clinical applications. Several research directions are currently ongoing in my group:
Donor-less Blood: The shortage of available blood is a constant and critical problem necessitating continual blood drives by agencies such as the Red Cross. We have demonstrated in our scientific paper (Nature Methods, 4:501-509, 2007) that hemangioblasts, a precursor to multiple cell types, can be produced from human embryonic stem cells on a large scale under serum-free conditions. Further, we have been able to show that these hemangioblasts can give rise to both hematopoietic and vascular cell lineages. Importantly, they can be used to create large quantities of erythrocytes (red blood cells), which carry oxygen to tissues throughout the body (Blood, 112:4475-4484, 2008). With our patent-protected technology we are working to produce a donor-less universal blood supply in limitless quantity to treat patients with rare blood types or in emergency situations such as for traumas or on the battlefield.
Donor-less Blood Platelets: Blood platelets are important for clotting and are used to treat a variety of illnesses requiring constant transfusions. Despite this critical need, there is a shortage of available platelets. With our hemangioblast technology we have developed a novel system to efficiently generate megakaryocytes from human embryonic stem cells. Megakaryocytes are bone marrow cells that are responsible for the production of platelets. Other researchers have been able to produce platelets but only by using serum or stromal cells which are animal-derived products. Our megakaryocyte technology produces a safe, reliable source of blood platelets free of animal products.
Dr Shi-Jiang Lu
Donor-less Bone Marrow: Bone marrow is used to treat diseases such as leukemia as well as for cancer patients requiring bone marrow replacement. With our hemangioblast technology we are working to see if transplanted hemangioblasts that we have derived from embryonic stem cells have the capability to grow in a recipient’s bone marrow and produce new bone marrow. Since these cells can be derived in large quantities under serum-free and reproducible conditions, the use of these cells would not be limited by availability, but rather the cells could be grown and differentiated for the precise clinical requirement of the individual with the potential for multiple infusions over the lifetime of the patient if required. For hemangioblasts from human embryonic stem cells, the ability to create banks of cell lines with matched or reduced incompatibility could potentially reduce or eliminate the need for immunosuppressive drugs and/or immunomodulatory protocols altogether. Inasmuch as induced pluripotent stem cell-derived hemangioblasts could be produced from a patient’s own cells, tissue incompatibility could be eliminated completely to avoid a major source of transplantation-related complications.
Retinal Vascular Therapies: Three major eye diseases associated with abnormalities in retinal vasculature (blood circulation in the eye) are glaucoma, diabetic retinopathy, and retinal vein occlusions. All three of these devastating diseases are leading causes of blindness. Glaucoma alone affects over three million people in the United States and about 40% of Americans diagnosed with diabetes have some stage of diabetic retinopathy. We have shown that when hemangioblasts, derived from human embryonic stem cells are injected into the eyes of mice they are capable of repairing damaged retinas and partially restoring vision (Nature Methods, 4:501-509, 2007 and Regenerative Medicine, 4:37-47, 2009). We are working to produce hemangioblasts on a large scale, differentiate them into the cells necessary for eye treatment, and begin a clinical trial to test the efficacy of these cells for the treatment of eye diseases.
Cardiovascular Therapies: Each year, about 1.1 million people in the United States have heart attacks and almost half of them die. We have shown that injection of hemangioblasts, which we have derived from human embryonic stem cells, into mice experiencing induced heart attacks has reduced the mortality rate by 50%. While the mechanism of this success is unknown we suspect it is due to the ability of these hemangioblasts to restore blood flow to areas damaged by heart attack. We are working to study its effectiveness in rats, a more complex model than mice, and thus more similar to humans. The therapeutic potential of this treatment is enormously promising.
Ischemic Vascular Therapies: Ischemia is a condition in which blood flow (and thus oxygen) is restricted to a part of the body. In its most severe form it can cause death. Patients suffering from diabetes can experience ischemia of the limbs requiring amputation. Our studies have demonstrated that injecting hemangioblasts into the ischemic hind limbs of mice has restored the blood flow in those areas to near normal levels. In other studies we have shown that introducing the hemangioblasts into mice wounds results in significantly enhanced healing. We are working to study the effectiveness of this treatment in rats in order to test whether hemangioblasts will be suitable for treatment of ischemia and wounds caused by a number of diseases, such as diabetes.
What was your experience of the OCT4, SOX2, NANOG and LIN28 antibodies and of Proteintech in general?
I tested the four antibodies, all of them are excellent. Most antibodies from Proteintech are excellent and your service is also outstanding. I always recommend my colleagues to Proteintech.
Why did you pursue a career in scientific research?
When I was a college student, to be a scientist was my dream. There was no other career at that time that attracted me the most.
Name one high and one low of your career so far.
Low: Grant reviewer’s comments that “Human ES cell lines are available, why are you using monkey ES cells for this research”: The fact is that the US government has not approved the use of federal funding for human ES cell research. When I resubmitted the proposal including human ES cell lines, the reviewers came back: “You have used monkey ES cells in your research for several years, why do you want to switch to human ES cells”.
High: Half a year after joining Advanced Cell Technology, I discovered and identified hemangioblasts derived from human ES cells.
If you could give just one piece of advice to a young PhD student, what would it be?
Be patient and concentrate on the research you are interested in. Award will come sooner or later.
What do you think will be the most important development in your field in the next decade?
The establishment of safe and authentic human iPS cell lines that are comparable, if not identical, to human ES cell lines. The differentiated derivatives from these safe iPS cells will be used in clinical settings.
What’s your favorite Proteintech antibody?
Anti-human CD31 (PECAM1) antigen antibody.
Who’s your most respected scientist?
Dr Fred Sanger who developed both protein and DNA sequencing.
Western blot or immunofluorescence?
I’ve done a lot of immunofluorescence stains on cells and tissues, sometimes you have to be aware of false positive signals. As for WB, you need a lot of material to start. You also can not tell the location of the protein in a specific cell.
PC or Mac?
I always use PC, no Mac experience.
Monoclonal or polyclonal?
No preference, what I care the most is the specificity.
Science or Nature?
No preference, both are excellent journals.
http://proteintech.wordpress.com/2010/05/25/interview-with-dr-shi-jiang-lu/
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