December 8, 2009

Dr. Elizabeth Fenjves of DRI

by

HAT TRANSCRIPT – Elizabeth Fenjves, Ph.D., Director of Gene Therapy at the Diabetes Research Institute (September, 14, 2006)

Want to be a guest speaker contact: Gina

Jon : (16:59): Welcome to the Diabetes Talkfest chat room!

AllisonBlass : (16:59): Should we have a drumroll first?

Jon : (17:00): Tonight we are chatting with Elizabeth Fenjves, Ph.D. Dr. Fenjves is Director of Gene Therapy at the Diabetes Research Institute. She is also an Associate Professor of Medicine and Pediatrics at the University of Miami.

Jon : (17:00): Dr. Fenjvesโ€™ research over the last 10 years has been focused on exploring the transfer of therapeutic genes to treat metabolic disorders. Her lab has been researching two major areas of investigation.

Jon : (17:00): Dr. Fenjves has published her findings in journals such as Human Gene Therapy, Diabetes and Transplantation. She holds an independent research grant from the American Diabetes Association and is a participant in a Center Grant from the Juvenile Diabetes Research Foundation.

Jon : (17:01): She is an active member of the American Society for Gene Therapy, The International Society of Transplantation and The American Transplantation Society.

Jon : (17:01): Welcome Dr. Fenjves

Ellen : (17:01): I’ll add that Dr. Fenjves is also very beautiful, inside and out…always approachable, always willing to answer questions and have people visit her lab.

Jon : (17:02): Go ahead with the questions

gina : (17:02): Let the questions begin!

Elizabeth Fenjves, Ph.D : (17:02): Wow thank you so much Ellen! I guess we can all use that…but tonight it feels particularly good

Ellen : (17:03): I’d like to know what got you interested in diabetes research per se

gina : (17:03): haha i was just going to ask that

gina : (17:03): yes why diabetes

gina : (17:03): and not cancer or aids or something?

Elizabeth Fenjves, Ph.D : (17:04): I was always interested in metabolic diseases and the idea that we could correct them by adding genetic material. Unfortunately diabetes is such a complex disorder that one gene won’t correct it. But the idea of combining gene therapy with metabolic disorders is just fascinating to me.

sue62 : (17:04): my md is also a teacher as well as a endocrinologist
.
Elizabeth Fenjves, Ph.D : (17:05): That’s wonderful because someone like that understands the current research

sue62 : (17:05): yes he does

gina : (17:05): can you explain a little bit about what exactly you do at the DRI

sue62 : (17:05): hes into cell biology – in addition to other things

Acroyear : (17:06): Elizabeth, how will the new reserch being done by the Lajolie Institute help us?? Encapsulating beta cells so we only have to do 1 shot a year potentially??

Elizabeth Fenjves, Ph.D : (17:06): Of course. What we are interested in is transplanting pancreatic islets into type 1 diabetics that can’t control their insulin. The problem is that the beta cells die in the transplant setting (the liver)

ann : (17:06): ok, here I go.. I have been dx last month.dR put me on Metformin 1,000 at dinner. Every afternoon around noon I get nausea.. every day…is this from my blood sugar or the meds….Also when I go high I get the sweats…is that normal…..?

Elizabeth Fenjves, Ph.D : (17:06): My lab is primarily interested in protecting the islets and the beta cells by inserting new protective genes into them.

Ellen : (17:07): I see that you are working on gene transfer with transplanted islets, is there any research being done to use gene therapy as a stand alone cure for diabetes without islet transplantation?

AllieB2 : (17:07): is that approach more effective than encapsulation, Dr. Fenjves?

Elizabeth Fenjves, Ph.D : (17:07): Ann I’m going to let someone else answer that because I’m not an MD.

Elizabeth Fenjves, Ph.D : (17:08): Encapsulation hasn’t worked well yet because the cells die for lack of oxygen. So you protect them from the immune attack but they die anyway.

gina : (17:08): How will you fix them from dying?

Acroyear : (17:08): if that is so…how many shots would we look at getting in a year?

Acroyear : (17:09):
and how far along are we at making our very own beta cell transplants available so we don’t have to have any anti-rejection drugs??

Elizabeth Fenjves, Ph.D : (17:09):
With gene therapy weโ€™re trying to protect the islets by inserting a protective gene. For example ERYTHROPOIETIN (EPO), which is used by athletes, will protect islets from dying.

sue62 : (17:10): have you studied people with more than i immune problem in realtionship to the diabetes?

Elizabeth Fenjves, Ph.D : (17:10): We’re pretty far from not needing anti-rejection drugs. We still use cadaver islets. One day we’ll be able to make islets from stem cells.

1955dm : (17:10): For what conditions has gene therapy been clinically useful, so far?

AllieB2 : (17:11): is ERYTHROPOIETIN a steroid?

shelleyk : (17:11): Dr. Fenjves, I am reading some of your papers using adenoviral and retroviral vectors for gene delivery. It is very interesting. Are there many people in your group, or elsewhere that you know of that are doing preventative research vs. treatment as well?

Elizabeth Fenjves, Ph.D : (17:11): For melanoma and for severe combined acquired immunodeficiency (SCID) which is the boy in the bubble disease

Acroyear : (17:11): why can we not make/take islets from our own bodies and make a warehouse of stored islets??

sue62 : (17:12): in my case i have hashimots as well as type 2 diabetes and theres considering fms autoimmune as well

shelleyk : (17:12): Isn’t there a group in Boston working on using other types of cells to produce insulin?

Elizabeth Fenjves, Ph.D : (17:12): EPO is not a steroid. It’s a naturally ocurring hormone that we all make to protect our red blood cells. It turns out it protects lots of other cells too..

Elizabeth Fenjves, Ph.D : (17:13):
Yes there is a group in Boston and one in Houston too. But so far it’s so difficult to make a cell that is glucose responsive. Any cell can be made to secrete insulin but not in a glucose responsive way.

gina : (17:14): is it possible in the near future that maybe my sister or someone in my family would be able to donate their cells to me?

Acroyear : (17:14): why can we not make/take islets from our own bodies and make a warehouse of stored islets??

shelleyk : AllieB2 (17:15): There seems to be many more groups working on type II vs. type 1, do you find this to be the case?

Elizabeth Fenjves, Ph.D : (17:15): There is one case where this was done however unfortunately the graft failed after a short while.

AllieB2 : (17:15): there are many more type IIs than type 1s ๐Ÿ™

Elizabeth Fenjves, Ph.D : (17:15): There is a lot of money being collected for type 2 at this point because it’s becoming such an epidemic in the world.

megan : (17:15): how long do islet transplants in current trials tend to last/

gina : (17:15): yea there are like 8 million just in new york ha

Ellen : 1955dm (17:16): Hopefully a cure for type 1 will also help those with type 2

AllieB2 : (17:16): but the research efforts nowadays are so progressive– I’m thrilled we have experts working on it, like Dr. Fenjves!

shelleyk : Elizabeth Fenjves, Ph.D (17:16): What about the generation of islets from stem cells, which theoretically may not be rejected?

Elizabeth Fenjves, Ph.D : (17:16): Islets have lasted in recipients up to 10 years. And yes there are overlaps in the disease cure approaches however type II as you know does not have the autoimmune component

Elizabeth Fenjves, Ph.D : (17:17): Stem cell research has exciting potential but there are still many issues. Certainly there is the political problem of not getting funding. But apart from that so far most stem cells have the potential of becoming carcinogenic. So we have to find ways

Acroyear : (17:17): that is stupid Type ii’s being epidemic..its the type 1’s that have all the problems and cause the strin on health care..Most of the type II’s should not have even been diabetic if they had taken care of themselves in the 1st palce

Elizabeth Fenjves, Ph.D : (17:17): to grow them, push them into becoming islets without turning cancerous and finally transplanting them. A lot of work to be done…

megan : (17:17): With stem cells, I understand we could have islets with no need for anti-rejection meds since our body recognizes them as our own. However, my immune system attacked my first set of islets. Even if I get another set through stem cell research, won’t those antibodies still be there?

sue62 : (17:18): so type 2 isnt autoimmune ?

megan : (17:18): no, type 1 is immune

Elizabeth Fenjves, Ph.D : (17:18): Yes megan you have the antibodies there but if the stem cells came from you there would hopefully be no rejection.

Elizabeth Fenjves, Ph.D : (17:19):
No type II is not autoimmune but type I is. In type I your own cells (the T cells) kill the beta cells in the islets.

Jon : (17:19): What is your biggest obstacle when trying to move forward with your research?

gina : (17:19):
****JUST A REMINDER PLEASE DO NOT PRIVATE MESSAGE DR. FENJVES****

beth : (17:20): i had a text book that said type 2 was autoimmune

sue62 : (17:20): just like hashimotos kills the thyroid system

beth : (17:20): but i am sure it was a mistake

pookas : (17:20): Why can’t stem cell research be privately funded? Because of the laws?

shelleyk : Elizabeth Fenjves, Ph.D (17:20): I actually have two questions, if a young scientist wishes to get into doing diabetes research, do you think there are a lot of opportunities?

Elizabeth Fenjves, Ph.D : (17:20): Our biggest obstacle is that we need to insert many genes. Diabetes isn’t simple and to insert more than one gene is so difficult.

Heather : (17:20): Dr. Fenjves, do you know what signals the body sends out that destroys the islet cells in Type 1 diabetics? I’m just now taking a microbiology course and was curious

Ellen : 1955dm (17:21): Stem cell research can be privately funded. In fact, when I make donations to DRI, I often ear mark my donation to go to stem cell research because it cannot receive Federal funding.

Acroyear : (17:21): If it is a money issue and a politics issue for those people that believe that stem cell research is against god, I say to them wake up and let those of us that need the help get it. We need more research, and more money

Elizabeth Fenjves, Ph.D : (17:21): There are a lot of opportunities to do research in diabetes because it’s getting more attention and funding. In terms of the question about stem cell, we get private funding for it at the DRI

gina : (17:22): **GIVE DR. FENJVES A MINUTE TO ANSWER YOUR QUESTIONS

Elizabeth Fenjves, Ph.D : (17:23): For Heather, we donโ€™t know exactly what the signals are we just know that there are both environmental and genetic predispositions. We also know that sometimes an infection can start a cascade that is damaging to a lot of cells in the body.

Elizabeth Fenjves, Ph.D : (17:23): Don’t worry GIna I’m a pretty fast typist…I started out as a temp secretary!

Heather : (17:23): thank you!

1955dm : (17:23): You mentioned risk of cancer with stem cells, but isn’t this a potential risk with any gene therapy, also?

AllieB2 : (17:24): Dr. Fenjves- if the autoimmune attack on beta cells is corrected, will the genetically protected beta cells for transplantation need a considerable amount of tweaking to survive?

Elizabeth Fenjves, Ph.D : (17:24): Not the way we do it. We do it outside the body, we actually insert the genes and make sure they are working before we transplant. The only issue with cancer and gene therapy is when the gene is inserted “in vivo” into the body.

megan : (17:24): trading diabetes for cancer? that’s encouraging…

Ellen : 1955dm (17:25): What studies in xenotransplantation are being done at the DRI?

Elizabeth Fenjves, Ph.D : (17:25): Yes Allieb2 because you have inflammation, you have cytokines that want to kill these new cells, you have “anoxia’ which is insufficient oxygen so there are lots of other attacks.

Elizabeth Fenjves, Ph.D : (17:26): No xenotransplantation yet. We are looking at pig islets and have used them for non-human primates but they are not being considered yet for people. In Mexico they’re doing it but in the US we’re a long way.

AllieB2 : (17:26): what a hostile environment we have! or maybe our immune systems work too hard ๐Ÿ˜‰

Elizabeth Fenjves, Ph.D : (17:27): Yes that’s well put. Very hostile and not at all interested in these new cells we’re putting in there that don’t belong.

megan : (17:27): does this hyperactive immune system put diabetics at higher risk for allergies, or is that a different type of immunoglobin?

sue62 : (17:28): what makes one person susceptible to an auto immune problem over another even in the same household

Ellen : 1955dm (17:28): Do you think you could use similar gene transfer with porcine islets to prevent rejection ?

pookas : (17:28): So we KNOW yet if an infection or virus [or a history of certain viruses] PLUS genetics triggers the Type 1, especially in children?

megan : (17:28): I know allergies are IgE, but I can’t recall what autoimmune diseases are

shelleyk : Elizabeth Fenjves, Ph.D (17:28): There is some gene therapy research being done at my school as well (on oral cancers though), they have issues of targeting the virus to specific cell types in this case cancer. Do you have targeting issues as well?

Elizabeth Fenjves, Ph.D : (17:28): That’s different, not the same antigens.

Elizabeth Fenjves, Ph.D : (17:29): We don’t KNOW but there are lots of people in the field that suspect that an infection often triggers the whole cascade

pookas : (17:29): Sorry, I meant “Do we know”

gina : (17:29): you mean that triggers diabetes in general

pookas : (17:29): My son got it RIGHT after having Scarlet Fever. Is there a way to know for sure?

Elizabeth Fenjves, Ph.D : (17:30): Auto immune simply means that you attack yourself with your immune system. That for some reason your own T-cells that should protect you from foreign antibodies suddenly think your beta cells are foreign

AllieB2 : (17:30): I got type I after I had the chicken pox

sixuntilme : (17:30): I was diagnosed right after I had a four day virus with an intense fever.

Heather : (17:30): it is very common to have the disease brought to the surface after being ill

Elizabeth Fenjves, Ph.D : (17:30): There are people working on trying to figure that out. They are called epidemiologists and they are looking at how common it is that an infection triggers a disease like this.

gina : (17:31): I got it right after my 25th birthday

shelleyk : (17:31): I also was sick with flu symptoms before I was diagnosed. It seems to be common here

beth : (17:31): Certain autoimmune disorders (in terms of age at onset) are more common in the elderly โ€“ and some in the young why ?

pookas : (17:31): My son also had Cocksaxi [sp?] when he was 2.

sue62 : (17:31): i got thyroid after i hit puberty – it wasnt dxd till years later

Elizabeth Fenjves, Ph.D : (17:32): Good question Beth. The immune response in the elderly is always weaker. However in autoimmunity the young are equally vulnerable.

pookas : (17:32): Are Type 1’s more prone to viruses? In your opinion/research?

Elizabeth Fenjves, Ph.D : (17:32): It doesn’t appear that Type 1 are more prone to other diseases.

sue62 : (17:33): not even auotimmune ones?

gina : (17:33): why would a person that is 25 years old develop type 1 do you think

beth : (17:33): maybe they were lucky to avoid the env. trigger for a long time

pookas : (17:34): It seems my son picks up EVERY virus in the school even if only one other child has it. I thought there could be a connection?

Elizabeth Fenjves, Ph.D : (17:34):
There are certain genes that predispose you and certain genes that protect you. The actual reason as to why at a certain point is really hard to understand but maybe the triggers weren’t there earlier even if the predisposition was.

beth : (17:34): did he go to day care

Heather : (17:34): they have started talking about a type 1 1/2 now in older adults

AllieB2 : (17:34): Dr. Fenjves- is BCG a virus? and if so, would it be a virus worth testing for gene therapy before transplantation?

pookas : (17:34): Preschool, but the viruses started much earlier.

pookas : (17:35): He was in school 3 days and had a cold already.

sue62 : (17:35): are you more predisposed too illnesses/diseases if your in your family tree you had relatives related BEFORE they got married and then got married?

Elizabeth Fenjves, Ph.D : (17:35):
I don’t know too much about BCG although I know some research is being done on it. We do very good virus testing before all our transplants and have never had a problem with that.

shelleyk : (17:36): What exactly is BCG?

AllieB2 : (17:36): it was a vaccination they gave for TB, many years ago

Elizabeth Fenjves, Ph.D : (17:37): The marriage between members of the same family is a risk because we all carry certain genes that only express as disease if both parents have them. Of course the likelihood of related people having the same “bad” gene is higher than a random person from the population

Ellen : (17:38): Dr. Pugliese was studying the development of the thymus and its relationship to the cause or onset of type 1 – is that still being looked at?

Elizabeth Fenjves, Ph.D : (17:39): Yes it is. I was going to suggest that you invite him one night. He knows a lot about the predisposing genes for type I

megan : (17:39): Dr. Fenjves- someone mentioned type 1.5 earlier

megan : (17:40): since that is autoimmune as well, would a cure for type 1 likely help those with 1.5 also?

sstrumello : AllieB2 (17:40): out of curiosity, will you guys/gals discuss this in more detail at the NYC researchers presentation in October?

tomahawk134 : (17:40): yes I am interested in learning about 1.5?

sue62 : (17:40): how would they differ?

shelleyk : (17:40): Which viruses are you using for your gene therapy studies?

Elizabeth Fenjves, Ph.D : (17:40): It’s very new and not fully accepted nomenclature. I think as kids start getting type II and older adults type I there is a blurring between the lines.

tomahawk134 : (17:41): and the blurring is 1.5?

AllieB2 : (17:41): i thought they were conducting blood test screenings to identify if the specific class of t-cell that attacks the beta cells is present to determine if it is type 1 of type 2. Maybe I misunderstood?

pookas : (17:41): That makes sense about the 1.5.

Ellen : (17:41): How much did the tragedy of gene therapy from Univ. of Penn, set back your research with gene therapy? Do you think it will slow its acceptance?

Elizabeth Fenjves, Ph.D : (17:42): I use primarily a “lentivirus” which is very useful because it infects non dividing cells. Islets don’t divide so it’s not simple to get genes into them. These are really good because of the fact they are safe.

bethy : (17:42): Agreed about the nomenclature bc ppl claim it means diff things ie 1.5 is lada 1.5 is mody โ€“ no one seems to be able to decide

Elizabeth Fenjves, Ph.D : (17:42): U Penn gene therapy was a horrible thing all around. It killed a young man unnecessarily and it set back the field by 20 years also unnecessarily. VERY SAD!

Ellen : gina (17:43): The Sept 2006 issue of Diabetologia (I think that issue) has an article on “declassifying diabetes”

Elizabeth Fenjves, Ph.D : (17:43): However there are recent results with melanoma and gene therapy that are so promising that we may be back in “business”

shelleyk : (17:43): I helped a lab at my school use a lentiviral vector to infect islets in culture. I don’t know what they ended up doing with it though; I just made the virus for them and had to rotate in another lab.

bethy : (17:44): Why are Caucasians more prone to t1 ?

Elizabeth Fenjves, Ph.D : (17:44): Wow Shelley come and work in my lab. That’s an amazing project. Did you enjoy doing it?

gina : (17:45): maybe the diabetes talkfest connected you two !!

gina : (17:45): lol

pookas : (17:45): Do you see any connection between blood types in the dx of Type 1’s? My husband [non-D] and son [D} have the same blood type and the type 1 is from his side, yet my older son is my blood type w/ no D yet. We haven’t had him tested for the antibodies.

Elizabeth Fenjves, Ph.D : (17:45): Pookas question is perfect for Dr. Pugliese. I think you defintely should invite him.

bethy : (17:46): is insulin a 49 amino acid peptide?

gina : (17:46): elizabeth maybe you can help me to contact him?

tomahawk134 : (17:46): Dr. Fenjves why are Native Americans more pre-disposed to Diabetes?

bethy : (17:46): or how many amino acids does it have

Ellen : gina (17:46): I can help with that too Gina ๐Ÿ˜‰

pookas : (17:46): They are both O- and my other son and I are A-.

gina : (17:46): ok thanks

Elizabeth Fenjves, Ph.D : (17:46): Yes native americans are highly predisposed. And I’d be happy to connect you to Dr. Pugliese.

shelleyk : (17:47): Yes, I actually miss virology a lot! I am finishing up my PhD in microbiology, hopefully in two months, I ended up choosing a lab working with HSV-1 and CMV over the diabetes lab because they were doing more typeII and insulin signaling, Now I regret it.

tomahawk134 : (17:47): Please that would be extremely helpful
Heather : (17:47): as I understand it there is much less of a genetic component with type 1

megan : (17:47): ugh, i hated microbiology, but pathophysiology was interesting

bethy : (17:47): native americans are highly predisposed to type II not type I

Elizabeth Fenjves, Ph.D : (17:47): Where are you getting your Phd?

shelleyk : (17:48): SUNY Upstate Medical University

tomahawk134 : (17:48): based on what bethy?

shelleyk : (17:48): In Syracuse, NY

Elizabeth Fenjves, Ph.D : (17:48): Great school. I got mine in SUNY Stony Brook.

megan : (17:48): I live in Buffalo

AllieB2 : sstrumello (17:48): Great School!!! 5 minutes from my house

gina : (17:48): elizabeth are you from NY?

gina : (17:48): thats where i am from long island

bethy : (17:48): Poor tolerance for the food that European people have been eating for a longer time ?

shelleyk : (17:48): :o) And now you are in sunny Florida!

bethy : (17:48): Maybe

sstrumello : shelleyk (17:48): you could always go into pharmaceutical research, shelly … only big pharma spends more on marketing than they do on research, and research into type 1 treatments are almost non-existent

bethy : (17:49): that stands for state university of NY

bethy : (17:49): right ?

gina : (17:49): yes

Elizabeth Fenjves, Ph.D : (17:49): I’m from Venezuela. But I came to the US for my education and ended up staying here.

tomahawk134 : (17:49): Hummm Bethy I am sure that may be a contributor to Type 2

shelleyk : (17:50): yes, I know. I actually am going to be doing some work with Bristol Myers Squibb starting the first of the year… but not on diabetes. Anti-cancer drugs instead

tomahawk134 : (17:50): but many of my relatives are Type 1

bethy : (17:50): All aboriginal ppl are more prone to type ii

gina : (17:50): elizabeth do you want to tell us anything else about what the DRI is working on

bethy : (17:51): Polynesians, aboriginal Australians Inuit

bethy : (17:51): well a lot of ppl say they have type 1 bc they take insulin

Elizabeth Fenjves, Ph.D : (17:51): WE are working on many approaches to keep islets alive. One is making special medias that are actually patented by the University of Miami. We are also putting proteins into the cells using “protein transduction”

pookas : (17:51): Thank you Dr. for talking w/ us!

bethy : (17:51): its a common mistake

tomahawk134 : (17:52): A comment Dr. Thank you for taking the time to address us

Ellen : (17:52): How is it going with the device that you had featured on the DRI mainpage, similar to Dr. Valdes device – a macro device? Did you use sertoli cells in it as well as islets?

tomahawk134 : (17:52): that is true bethy

Elizabeth Fenjves, Ph.D : (17:52):
We are also using stem cells to try and coax them to become islets. And my lab is interested in adding certain “extra cellular matrix proteins” to make islets do better in culture. We are doing this with a company and getting really lovely results.

tomahawk134 : (17:52): I would like to talk to some more on this Bethy

bethy : (17:52): okay

tomahawk134 : (17:53): I need to conclude for the evening I will look for you on the forum

Ellen : gina (17:53): Really lovely results {lol_smiley}

Elizabeth Fenjves, Ph.D : (17:53): About the Valdez device we weren’t able to duplicate many of his results. Yes we did put sertoli cells.

bethy : (17:53): do you know what Pancreastatin is ?

sstrumello : shelleyk (17:53): any research into cultivating knock-out pigs? There was some news this week on xenotransplantation into primates (monkeys) recently ***

AllieB2 : (17:54): Dr. Fenjves– are you allowed to tell us the name of the company? (for those of us who are always looking for promising *investment* opportunities?)

Elizabeth Fenjves, Ph.D : (17:54): It was such a pleasure to talk to all of you. Best of luck and don’t hesitate to write any of directly at the DRI. We love visitors and interested people.

megan : (17:54): thank you Dr. Fenjves

sstrumello : Elizabeth Fenjves, Ph.D (17:54): I hope to see you at the NYC research presentation in October!!

Ellen : (17:54): Thank you so very much for your generosity of time and spirit.

sstrumello : Elizabeth Fenjves, Ph.D (17:55): Thanks for joining us this evening!

shelleyk : (17:55): Not that I know of, but again I am not too up to date on current diabetes research (too busy writing my thesis

Elizabeth Fenjves, Ph.D : (17:55): No i’m sorry I can’t tell you the name but I wouldn’t invest right now anyway. We are doing work with Amylyin that you probably know has generated an exendin like molecule.

Jon : (17:55): Thank you for being here tonight, Dr. Fenjves!

AllieB2 : Elizabeth Fenjves, Ph.D (17:56): Yes, I love Amlyn these days ๐Ÿ˜‰

Elizabeth Fenjves, Ph.D : (17:56): my pleasure, good night.

AllieB2 : Elizabeth Fenjves, Ph.D (17:56): Symlin is a blessing!

AllieB2 : Elizabeth Fenjves, Ph.D (17:56): Thank you Dr. Fenjves!

Jon : (17:56): You are welcome back any time

Jon : (17:57): To find out more about the Diabetes Research Institute and Dr. Fenjves go to <a href=”http://www.diabetesresearch.org”>www.diabetesresearch.org</a>