Welcome to Cho Lab of Pharmaceutical Chemistry. As the name implies, this lab adopts chemical approaches in solving biopharmaceutical problems involved in drug delivery, particularly cellular delivery of nucleic acids. Our strategies range from design and synthesis of a novel class of surface-active agents that would permeabilize endosomal membrane as a consequence of endosomal acidity (Asokan and Cho, 2005; Asokan and Cho, 2002; Asokan and Cho, 2003; Asokan and Cho, 2004; Chen et al., 2003) to exploiting long circulatory life of endogenous immunoglobulins as drug carrier targeted to solid tumors (Palma et al., 2007; Palma et al., 2005; Rehlaender and Cho, 1998; Rehlaender and Cho, 2001a; Rehlaender and Cho, 2001b). We are continuously exploring new approaches as one can see below rendering this lab unique with the breadth of research projects. Thus, if one wishes, he/she can learn a great deal through “osmosis” on a subject related to but rather independent of his/her own research project. The downside may well be a feeling of “loneliness,” but that is why the door of this PI is always left open. This PI is one of the most easily accessible professors on the campus.

As in any organization, a lab is perhaps best described by people in it. This welcome note thus will introduce who is doing what rather than which project slaves whom.  This time last year, i.e., during the summer of 2007, this lab consisted of four graduate students and one post-doctoral fellow. This is a good steady-state level this PI wishes to maintain. Since then David Gaul, PhD, has left for Duke (of all places). At this writing (August of 2008), we are looking for a PhD in organic chemistry for his place. Since John An is about to defend his final thesis, we plan to accommodate at least one new graduate students. Two new students, Kayla Knilans (BS in chemistry from U of Wisconsin at Madison) and Tianxiang (Kevin) Han  (MS in pharmaceutical sciences from Peking U), have expressed interest in doing lab rotation in my lab during Fall semester of 2008. Thus, dC/dt ~ 0 seems to be well maintained.       

Describing graduate students must start appearance and end with their inclination to music (or noise). Then there are hobbies, religion, working habit, taste toward opposite gender, drink of preference, and reading materials (when they do, that is). Based on the state of their hair and beard in the morning, one can perhaps speculate their sleeping pattern or shower schedule but we will not go there. Neither will we visit the argument on Obama versus Clinton versus Bush versus McCain. As you can see from our picture, we are about average in appearance but outstanding in health, intelligence, ambition, and appetite toward pizza and beer (especially when they are free).  The lab meeting begins at 5 PM every other Friday in Kerr Hall 1304 and finish at about 8 PM in Spank’s in downtown.  This is in addition to the 8 AM weekly individual discussion with each of lab members.

OK, junior first. Patrick Guley is at a most impressionable stage of adulthood. It appears that you can sell him almost anything and mold him anyway you wish. He is looking up other old timers but most of the time in a wrong way.  He clearly saw how messy others’ lab benches are and yet adopted the fashion in no time. He came clean and now has stubble on the chin. At present he is having a hard time to determine which of the two, all-out mustache and beard, i.e., Manchester-look (see below), or good old Don Johnson look of Miami Vice, would make him look tougher and “used.” Considering he was from the NC Math and Science School, which was to accommodate only “Smartest Children of the State”, entering chemical engineering program of Norte Dame must have been a reasonable expectation. Then, intrinsic intelligence aside, his GPA hit the bottom (not clear how it happened but one can guess) and suffered from it for a few years wondering around Appalachean trail in solitude (his hobby). Early this year he finally encountered an epiphany in Molecular Pharmaceutics and will become a new student this fall. In the mean time as a lab tech, he has been working on anti-HCV (hepatitis C virus) siRNA delivery. Our approach exploits so-called proton-sponge hypothesis and polymer-based carriers.

Michael Hackett, alias Manchester, has come here by way of the Huang Lab, where he wept along with tumor-bearing mice.  Majored chemistry at Case Western Reserve and somehow became a fan of Manchester soccer team, United Football Club. As a result, his self-promoting alias was born (yes, the one in UK for a guy from Ohio). So far he has shown an affinity toward ether, vacuum pump, radioactivity, head band, a pair of sunglasses (one of those wraparound things), and two dogs. This man is certainly a fast thinker and smooth talker, and people are accordingly advised of him as such. Although he is a big guy and does all heavy lifting in the lab, his light-footed movement (hasn’t bumped into anything yet) defies the Stokes-Einstein Equation on diffusion. We are re-visiting albumin as an endogenous drug carrier. Fatty acid chemistry is currently being modified such that its prodrugs still maintain a negative charge from –COOH. His preliminary isothermal titration calorimetry studies have yielded an astonishing result, far more exciting than we had anticipated. More materials are being prepared in solid-phase to confirm reproducibility. Once again, we have a chemistry rate-limiting project.  

Roland Cheung, biology-major from U of Maryland, used to chase migratory orioles in his previous life all the way down to Mexico but gone are such lazy-river days. His disposition is most “docile” among us and thus most popular among females. He is also most accommodating and altruistic, and thus tends to do what others seem to avoid. He is still in charge of Journal Club meetings. He sure looks like a Chinese and enjoys Chinese food, but his knowledge of China may be quite limited. He cannot handle beer and hence least threatening. Learning chemistry (separation chemistry to be exact) at the bench level has been an uphill battle for him but he seems to finally enjoy independent experiments; always glued to the only rotary evaporator in the lab. Good thing he is not possessive, or others could have had to take numbers and wait. He has designed and synthesized water-soluble crosslinkers that can be used in inverse microemulsion polymerization. They contain either disulfide or a tripeptide substrate of cathepsin B. This approach is coupled with the proton sponge effect mentioned earlier. At this writing, his chemistry component of his project is almost over. He is about to embark on cellular confocal microscopy and functional assay with polymerized nanogels that contains oligonucleotides.      

All said, the stability of this lab is certainly from senior students. After Jin Lee graduated last year, John An has been the man. Considering he entered PhD program in 2001, he is well qualified for this position. His efforts to adopt SELEX (systematic evolution of ligands by exponential amplification) and mRNA Display System in developing a novel class of drug carriers have not been very successful: theories behind these procedures are simple and straightforward but practice has been nothing but simple. We have learned some valuable lessons and now are marching forward. All said, this has holden his progress for at least one year. John has just submitted the draft of PhD thesis that he will defend on 8/15/Fri/08. We all pray for him. He has already begun his clinical fellowship and plans to eventually work for a government regulatory agency such as FDA in the future. He has pioneered three different exploratory lead-finding projects, one of which is Manchester’s project. The other two are directly related to nanoparticulate-based nucleic acid delivery although his work itself uses colloidal gold.  

All in all, we encounter our own shares of ups and downs but maintain a good faith on what we do and are always looking forward to challenging tasks. For students, it is usually the chemistry that controls the research progress. For this PI, it is the research funding. Two NIH grants expired by the end of 2007. Very fortunately the R01 grant application based on Enzo Palma’s PhD thesis has been successful: total approximately $1.5 M over a 5-year period will be available. We are all very pleased with the outcome especially knowing that it is from NCI, one of the toughest institute to get fund from nowadays. Another good news is that now this PI can control the music (noise) in the lab whenever he wants to. Manchester and Patrick gave him this ON/OFF wireless switch that can turn off their music (noise) a long way before he enters the lab: a SVAT Model WRC100 Remote A5 is about 2” W x 3” L x 0.5” T.  Finally, all names mentioned above can be contacted via e-mail. They will provide ins and outs of this lab, especially detailed description of agony associated with exams, irreproducible results, lack of sleep, car accident, bad food of cafeteria, flood from still apparatus, etc. If they are in good mood by chance when contacted, they may say a few good words on the PI. They may also explain how they sold the tread mill that has been in this PI’s home and what they plan to do with the cash from the transaction.

John An: john-an@email.unc.edu
Roland Cheung: roland@unc.edu
David Gaul: dgaul@email.unc.edu
Patrick Guley: pguley@email.unc.edu
Michael Hackett: mhackett@email.unc.edu

M. J. Cho: m_j_cho@unc.edu

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