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Niki M. Zacharias Millward, PhD

Present Title & Affiliation

Primary Appointment

Assistant Professor, Department of Cancer Systems Imaging, Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX
Associate Member, University of Texas Graduate School of Biomedical Sciences, Houston, TX

Dual/Joint/Adjunct Appointment

Assistant Professor, Bioengineering, Rice University, Houston, TX

Bio Statement

The goal of Dr. Millward’s lab is to use chemistry and biochemistry to design chemical probes to interrogate biological systems.   Her lab’s most recent research has been focused on studying metabolism and how metabolism is affected in cancer and during metastatic progression.   Her team’s research utilizes high field magnetic resonance to determine the metabolic profile of tissue and cells (steady-state metabolic profile).  The lab is particularly interested in using synthetic and bioorganic chemistry to develop new probes for enzyme activity and metabolic transformation that can serve as tools for fundamental research in biological networks. This research utilizes a new imaging technique, hyperpolarized magnetic resonance.  Hyperpolarization increases the sensitivity of magnetic resonance by over 50,000 fold and therefore allows for real time in vivo metabolism to be observed in tissue culture, in animals and eventually in patients. 

Research Interests

As a chemist, my goal is to use chemistry and biochemistry to understand the metabolism of cancer and use this knowledge to design metabolic imaging probes and develop these probes from the bench to the clinic.

We are specifically interested in creating hyperpolarized metabolic imaging agents for magnetic resonance (MR) imaging and spectroscopy and, we are interested in determining the metabolic profile of cancer cell lines and tumor tissue using high field Nuclear Magnetic Resonance (NMR). NMR and MR are both powerful methods of determining the metabolic profiles of cancer. Hyperpolarized contrast agents increase the sensitivity of conventional MR over 50,000 fold and have the potential for early detection and selection of therapies for individual cancer patients. The four areas of research my lab is currently working on are a) synthesis and polarization of new imaging and metabolic compounds using Parahydrogen Induced Polarization (PHIP) and Dynamic Nuclear Polarization (DNP) with compounds containing either the non-radioactive isotopes 13C, 15N, 29Si, or a combination of. These molecules are small molecules, larger nanoparticles, and polymers b) application of hyperpolarized molecules in in vivo applications to different mice models of cancer, neurodegenerative and cardiovascular diseases c) determining the metabolic profile of cancer cell lines and tumor tissue using high field NMR d) using bioreactors and 3D cell culture and hyperpolarized agents to interrogate the metabolic cycles of different cancer cell lines. 

Education & Training

Degree-Granting Education

2003 California Institute of Technology, Pasadena, CA, PHD, Chemistry
1997 Texas A&M University, College Station, TX, BS, Chemistry

Experience/Service

Academic Appointments

Assistant Professor, Department of Experimental Diagnostic Imaging, Division of Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX, 3/2012-5/2013

Honors and Awards

2011 Best Poster and Presentation Award in MRI Probes including Hyperpolarization II Session at World Molecular Imaging Congress
2011 International Society of Magnetic Resonance Annual Research Conference Student Stipend Award
2010 In Vivo Magnetic Resonance Gordon Research Conference Student Stipend Award
2000-2001 NIH Training Grant in Bioorganic Chemistry

Professional Memberships

American Chemical Society
Member, 1/2012-present
International Society for Magnetic Resonance in Medicine
Member, 8/2012-present

Selected Publications

Peer-Reviewed Original Research Articles

1. Zacharias NM, Chan HR, Sailasuta N, Ross BD, Bhattacharya P. Real-time molecular imaging of tricarboxylic acid cycle metabolism in vivo by hyperpolarized 1-(13)C diethyl succinate. J Am Chem Soc 134(2):934-43, 1/2012. e-Pub 12/2011. PMCID: PMC3262122.
2. Bhattacharya P, Chekmenev EY, Reynolds WF, Wagner S, Zacharias N, Chan HR, Bünger R, Ross BD. Parahydrogen-induced polarization (PHIP) hyperpolarized MR receptor imaging in vivo: a pilot study of 13C imaging of atheroma in mice. NMR Biomed 24(8):1023-8, 10/2011. e-Pub 4/2011. PMCID: PMC3240663.
3. Eastwood AL, Blum AP, Zacharias NM, Dougherty DA. A selenide-based approach to photochemical cleavage of peptide and protein backbones at engineered backbone esters. J Org Chem 74(23):9241-4, 12/2009. PMCID: PMC2953381.
4. Petersson EJ, Brandt GS, Zacharias NM, Dougherty DA, Lester HA. Caging proteins through unnatural amino acid mutagenesis. Methods Enzymol 360:258-73, 2003. PMID: 12622154.
5. Beene DL, Brandt GS, Zhong W, Zacharias NM, Lester HA, Dougherty DA. Cation-pi interactions in ligand recognition by serotonergic (5-HT3A) and nicotinic acetylcholine receptors: the anomalous binding properties of nicotine. Biochemistry 41(32):10262-9, 8/2002. PMID: 12162741.
6. Zacharias N, Dougherty DA. Cation-pi interactions in ligand recognition and catalysis. Trends Pharmacol Sci 23(6):281-7, 6/2002. PMID: 12084634.
7. Bekele H, Nesloney CL, McWilliams KW, Zacharias NM, Chitnumsub P, Kelly JW. Improved Synthesis of the Boc and Fmoc Derivatives of 4-(2'-Aminoethyl)-6-dibenzofuranpropionic Acid: An Unnatural Amino Acid That Nucleates beta-Sheet Folding. J Org Chem 62(7):2259-2262, 4/1997. PMID: 11671538.

Invited Articles

1. Suto MJ, Zacharias N. Neuronal nicotinic acetylcholine receptors as drug targets. Expert Opin Ther Targets, 4/2004.

Book Chapters

1. Bennett PB, Zacharias N, Nicholas JB, Sahba SD, Kulkarni A, Nowak M. Unnatural Amino Acids as Probes of Ion Channel Structure – Function and Pharmacology. In: Expression and Analysis of Recombinant Ion Channels: From Structural Studies to Pharmacological Screening. 2006.

Grant & Contract Support

Title: , Determining and Correlating the Metabolic Profile of Melanoma Cell Lines with iNOS Expression
Funding Source: NIH/NCI
Role: Principal Investigator
Duration: 12/28/2014 - 12/27/2015
 
Title: Glioblastoma Moonshot
Funding Source: MD Anderson Moonshot
Role: Co-Investigator
Principal Investigator: Amy Heimberger
Duration: 9/1/2014 - 8/31/2015
 
Title: Early Detection of Pancreatic Cancer In Vivo by Molecular Imaging of Lactose-functionalized
Funding Source: NIH/NCI
Role: Co-Investigator
Principal Investigator: Pratip Bhattacharya
Duration: 4/1/2014 - 3/31/2016

Last updated: 7/15/2015