Page 5 - Shimadzu Journal vol.3 Issue3

Insight from Customer

Professor Alexander (Leggy) Arnold from
Milwaukee Institute for Drug Discovery

We interviewed Dr. Arnold, aka Leggy Arnold, who is an Associate Professor in the Department of Chemistry and
Biochemistry, Principle Investigator of the Shimadzu Laboratory for Advanced and Applied Analytical Chemistry and
Founding Member of the Milwaukee Institute for Drug Discovery (MIDD) at the University of Wisconsin-Milwaukee
(UWM). One area of his research is focused to elucidate the biological and pharmacological role of vitamin D
receptor–coregulator interaction by using small molecule probes that in turn are developed into drug candidates for
metabolic disease and cancer. His lab supports high throughput screening, medicinal chemistry, biochemistry and
molecular biology. The relationship with Shimadzu started in 2014, when the “Shimadzu Laboratory for Advanced
and Applied Analytical Chemistry” was established within the MIDD.

Dr. Arnold, thank you very much for spending some In particular, our research is supported by the MIDD. Our director,
time for this interview. At first, could you outline the Dr. Douglas Stafford, worked in conjunction with Shimadzu to
research and let us know what discovery and establish an “Analytical Chemistry Center of Excellence” at the
achievements have been made so far? UWM. Dr. Stafford was able to secure funding from the University of
Wisconsin System for a Center concept to not only support basic
Our research is focused on the identification of new synthetic and
research across our campus, but also serve as a regional resource for
natural compounds that modulate the function of the vitamin D
industrial collaborations and chemistry education. Shimadzu was
receptor. The vitamin D receptor is a transcription factor that induces
very generous by providing matching funds in form of
the production of RNA molecules, which in turn are used to generate
instrumentation and long-term support and therefore enabled the
essential proteins in our body. The vitamin D receptor, as the name
establishment of one of the most sophisticated mass spectroscopy
implies, binds vitamin D and its metabolites. We have been working
facilities in the nation.
together with the NIH Chemical Genomics Center and applied high
throughput screening to find new compounds that modulate the
function of the vitamin D receptor. We have developed several
different compounds that bind the receptor directly or those that bind
the receptor surface to modulate the interaction with coregulatory
proteins that are essential for gene transcription. We observed that a
specific irreversible inhibitor class of compounds exhibited
antiproliferative effects. Based on that finding, we developed a
compound against leukemia and another compound that reduces the
growth of ovarian tumors.

Why are you interested in this research? What is the goal?
We are all familiar with vitamin D as an essential vitamin that prevents
bone diseases, improves kidney function and is an important molecule
for healthy skin and hair growth. The molecule that regulates the
majority of processes is the vitamin D receptor. I believe that we can
target the vitamin D receptor with small molecules to fight diseases
that need this receptor in order to thrive. One of the most used
chemotherapeutics in the United States for fighting breast cancer is How are our instruments helping you?
Tamoxifen. Tamoxifen is binding a closely related receptor called the
estrogen receptor. Like the vitamin D receptor, the estrogen receptor Our Shimadzu Laboratory for Advanced Applied and Analytical
is essential for many life processes. We are able to target this receptor Chemistry facility is equipped with a range of new instruments and is
with small molecules to successfully fight breast cancer. I’m convinced housed in a brand new 2,000 sq. ft. laboratory in UWM’s new
that that the vitamin D receptor has a similar potential and can be Kenwood Interdisciplinary Research Center. Our instrumentation
targeted by smart compounds to reduce the growth of tumors includes Shimadzu products such as the MALDI-7090 with AccuSpot
especially those that express high levels of this receptor like skin cells, and CHIP. We and other researchers are using this flagship MALDI
white blood cells, and many more. In addition, we continue our work TOF-TOF platform for proteomics. In particular, our group is
on the development of new treatments for kidney diseases, identifying the binding site of our irreversible VDR inhibitors. In
osteoporosis and immune diseases. addition, we are conducting metabolomic research by identifying new
catabolic products of vitamin D to determine their biological activity in
respect to the vitamin D receptor. Our group is interested in
Could you tell us why you chose Shimadzu as your pinpointing the most metabolically active tissues for the conversion of
partner when you established this new lab? vitamin D to the most potent ligand of VDR 1,25-dihydroxyvitamin D3.

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