Welcome to Cho Lab of Pharmaceutical Chemistry. 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 (Aravind 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).

With the unavoidable influx and vortex of high-volume R&D activities from the Program in Macromolecular Therapeutics (PMT) and Carolina Center of Cancer Nanotechnology Excellence (C-CCNE), part of this lab is also whirling around more collaborations with chemistry on one hand and biology on the other. These activities are further fueled by the Drug Delivery Discussion Group that was newly formed with Duke Biomedical Engineering folks when Leaf Huang arrived here and ever-expanding Journal Club meetings. In between these meetings and seminars, we seem to barely find time for bench works. Nonetheless, one research project clearly emerged is siRNA delivery using particulate drug carriers that are produced with water-soluble crosslinkers that can be cleaved in the endosome.

This lab consists of four graduate students and one post-doctoral fellow. This is a good steady-state level we wish to maintain. Earlier two students, one an old timer and the other rotation student, bowed out. Either the kitchen became too hot or the grass looked greener beyond this lab. David Gaul, PhD (left on the first row) is known as Christine’s better half since the latter of Huang Lab is more widely known on the hallway. David serves as a shoulder which others cry over with tough chemistry. He seems to possess an infinite capacity of accommodating others’ frustration while carrying out his own research on protamine-based plasmid DNA incorporation into polyplex. Michael Hackett (the big guy in the middle) has come here by way of Leaf’s lab, where he played with mice most of the time.  Majored chemistry at Case Western Reserve and somehow became a fan of Manchester soccer team, United Football Club. Yes, the one in UK in all places for a guy from Ohio……  Thus far he has shown a high affinity toward ether (lab smells good) and a pair of sunglasses (one of those sleek jobs). This man is certainly a fast thinker, but his argument may not always hold the H2O.

Roland, in front of David, has just passed Qualifying Exam Part II, oral defense of his project. As usual, he has just got stuck in chemistry again, separation to be exact. Once this hurdle is over, he will coast downhill with wind at the back. Currently he is in a market for a car: below $10,000 please. When he has a breakthrough in chemistry (i.e., when he feels all is well), he may tell you what happened to his brand new, black Honda just before the oral defense. Do not expect a pretty story though. All said, the stability of this lab is certainly from the two senior students Jin, the man under meditation in front of John,  and John. Jin is defending his PhD thesis on 5/30/Wed/07. At this writing in April, 2007, we have gone through all chapters except Chapters I (Introduction) and V (Further Studies).  It is truly amazing how much breadth his work has covered: ranging from synthesis of PEG conjugate of folic acid to enzymatic methylation of plasmid DNA for radioisotope labeling; pharmacokinetics of PRINT particles in normal and tumor-bearing mice to synthesis of diacrylate crosslinker that contains a –S-S- bond.

Our recent 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 ……… But we have learned many valuable lessons. John An’s misery loves companies. Contact John to share your own tears. He is the third man on the first row in our group picture. His latest setback was caused by a wrong product we received from one of the leading suppliers of siRNA. After a few failures in his chemistry with the expensive custom-synthesized ssRNA, he was able to establish that the material we received was wrong.  If this sort of misfortune is his fate, we may have to bring an exorcist. Indeed time has not been kind to him. After we sent convincing MALDI-TOF data, this specialty company has finally backed off and is re-synthesizing a less challenging compound at no cost.

All said, we have encountered own shares of ups and downs but are in 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 this year. An R01 grant based on Enzo Palma’s PhD thesis is pending with a great deal of preliminary data but its outcome is not a shoo-in. This grant will go to the NCI where the pay line is hovering around 10 percentile. There are simply too many smart scientists for the limited NIH budget. In this context alone, we sincerely hope that this country finds a new leader who will divert the $2.8 billions to supporting 2,800 five-year grants, rather than buying one B-2 bomber that we don’t know where to use. Now the cost of the war in Iraq is approaching $500 billion and they want to build a wall on the border with Mexico. My lament…..

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, bad food of cafeteria, flood from still apparatus, etc. If they are in good mood by accident when contacted, they may say a few good words on the PI.

John An: john-an@email.unc.edu
Enzo Palma: epalma@wfubmc.edu
Jin Lee: jinlee@unc.edu
Roland Cheung: roland@unc.edu
David Gaul: dgaul@email.unc.edu
M. J. Cho: m_j_cho@unc.edu

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