1. A Potential Global Role for Dipeptidylpeptidase 4
(DPP4/CD26) and Its Inhibition In The Regulation of
Hematopoiesis and Other Cell Systems
Hal E. Broxmeyer, PhD
Department of Microbiology/Immunology
Indiana University School of Medicine
Indianapolis, Indiana, USA

2. Disclosure: Hal E. Broxmeyer, Ph.D.
Financial interests to disclose
Consulting:
Cord Use - a public cord blood banking company - MSAB and
a founder of Cord Use Family Cord Blood Bank
Fate Therapeutics - Consultant

3. Since our initial scientific and clinical studies,
Broxmeyer et al Proc. Natl. Acad. Science USA 86:3828-3832,
1989
Gluckman, Broxmeyer et al N. Engl. J. Med. 321: 1174-1178, 1989
there have now been over 30,000 cord blood transplants
done to treat a wide variety of malignant and non-
malignant disorders with hematopoietic stem cells
Broxmeyer, Farag, Rocha. 2013. Cord Blood Hematopoietic Cell
Transplantation. In: Thomas’ Hematopoietic Cell
Transplantation 5th Edition (Applebaum, Forman, Negrin, Antin,
Eds) Wiley-Blackwell, England
Ballen, K.K., Gluckman, E., and Broxmeyer, H.E. 2013. Umbilical
Cord Blood Transplantation – the first 25 years and beyond.
Blood. In press

4. Goal
Understanding biology of HSC to enhance
transplantation engraftment:
• CD26/Dipeptidylpeptidase (DPP) 4 influence
on cytokine action, hematopoiesis, recovery
from stress, and engrafting capability
A more global role for DPP4

5. CD26/DPPIV (dipeptidylpeptidase IV)
cleaves dipeptides from the N-terminus
after a proline or an alanine
CD26/DPPIV
N- X1 - A/P2 - X3 - X4 … -C
Cleavage of substrates after
the N-terminal
pen-ultimate alanine or
proline
cleavage

6. Modulation of Hematopoietic
Stem Cell Homing and
Engraftment by CD26
K.W. Christophersen, Giao Hangoc,
Charlie Mantel and Hal E. Broxmeyer
Science 30:1000-1003, 2004

7. CD26/Dipeptidylpeptidase IV Negatively
Regulates Colony Stimulating Factor
Activity and Stress Hematopoiesis
Hal E. Broxmeyer, Jonathan Hoggatt, Heather O’Leary,
Charlie Mantel, Brahmananda R. Chitteti, Scott H. Cooper,
Steven Messina-Graham, Giao Hangoc, Sherif Farag,
Sara L. Rohrabaugh, Xuan Ou, Jennifer Speth, Louis M. Pelus,
Edward F. Srour and Timothy B. Campbell
Nature Medicine 18: 1786-1796, 2012

8. In addition to SDF-1/CXCL12 and a number of other
chemokines, there are other cytokines
that have putative CD26 truncation sites
Growth
Factor
Species Full length N-terminus
Predicted
Mass
Truncated N- Terminus
Predicted
Mass
GM-CSF
Human APARSPSPSTQPWEH… 14,469 ARSPSPSTQPWEH… 14,301
Mouse APTRSPITVTRPWKH… 14,112 TRSPITVTRPWKH… 13,944
G-CSF
Human TPLGPASSLPQSFLL… 18,661 LGPASSLPQSFLL… 18,463
Mouse VPLVTVSALPPSLPL… 18,940 LVTVSALPPSLPL… 18,744
IL-3
Human APMTQTTSLKTSWVN… 15,072 MTQTTSLKTSWVN… 14,904
Mouse ASISGRDTHRLTRTL… 15,673 N/A N/A
EPO
Human APPRLICDSRVLERY… ~37 kDa † PRLICDSRVLERY… ~37 kDa †
Mouse APPRLICDSRVLERY… ~36 kDa † PRLICDSRVLERY… ~36 kDa †
M-CSF
Human EEVSEYCSHMIGSGH… 18,403 * N/A N/A
Mouse KEVSEHCSHMIGNGH… 25,987 * N/A N/A
SCF
Human EGICRNRVTNNVKDV… 18,458 N/A N/A
Mouse KEICGNPVTDNVKDI… 18,298 N/A N/A
FL
Human TQDCSFQHSPISSDF… 18,050 N/A N/A
Mouse GTPDCYFSHSPISSN… 18,385 N/A N/A
* This may be in dimer form as well.
† Glycosylated protein.

9. Cytokine
Cytokine +
DPPIV(18 hrs)
Cytokine +
Diprotin A +
DPPIV (18 hrs)
GM-CSF IL-3
m/z14100 14600
Intensity
160
0
<14471>
m/z14100 14600
Intensity
50
0
<14473>
m/z14100 14600
Intensity
18
0
14301
14470
m/z2000 20000
Intensity
160
0
14471
m/z2000 20000
Intensity
120
0
15080
m/z14700 15200
Intensity
120
0
15080
m/z14700 15200
Intensity
40
0
14914
m/z14700 15200
Intensity
20
0
15085
Full Spectrum
14,471
14,471
14,301
14,473
15,080
15,080
15,085
14,914
Mass Spec Analysis of Human GM-CSF and IL-3

10. 0 10 20 30 40 50 60 70 80 90
Colony Formation by Human Cord Blood Cells
Control
DA w/ WASH
DA w/ NO WASH
Influence of Diprotin A Pretreatment of Human Cord Blood on Human
Cytokine Stimulation of CFU-GM Colony Formation
rhuGM-CSF (20)
rhuGM-CSF (10)
rhuGM-CSF (1)
rhuG-CSFmet (20)
rhuG-CSFmet (10)
rhuG-CSFmet (1)
rhuIL-3 (20)
rhuIL-3 (10)
rhuIL-3 (1)
rhuM-CSF (1000)
rhuM-CSF (100)
rhuM-CSF (10)
rhuFlt3L
rhuSCF
rhuG-CSF (20)
rhuG-CSFmet (20)

11. Influence of Diprotin A (DPA) Pretreatment of Mouse Bone Marrow
or Human Cord Blood on EPO Stimulation of BFU-E colony
Formation
Mouse Bone Marrow
Stimulated by Recombinant
Mouse (N=3) or Human (N=3) EPO
Human Cord Blood
Stimulated by Recombinant
Human (N=5) EPO
[Fold Increase of +DiProtinA / -DiprotinA]
a p<0.01 for +DPA compared to -DPA
0 0.5 1 1.5 2 2.5
a
a

12. • DPP4-truncated CSFs were much less active
than full length CSFs
• Truncated CSFs blocked the activity of their own
full length CSF form, acting as a dominant
negative form of CSF
additional information (in vitro)

13. Effects of CD26 -/- on Cytokine
Actions In Vivo.

14. Control
EPO: Full Length
EPO: Truncated
EPO: FL+T
+/+ CD26 -/-
0
2
4
6
8
10
12
14
16
(3.8X)
(1.4X) (1.3X)
(6.3X)
(1.6X) (1.8X)
*
*
*
*
*
*
*
* P<0.01, N=4/group; 10U EPO (FL, T) or 10U each FL or T s.c. Blood assessed 24 hrs later
Influence of EPO On % PB Reticulocytes

15. Effects of Full Length and Truncated rmuGM-CSF, Alone and in Combination,
on Absolute Numbers of Hematopoietic Progenitor Cells (HPC)
0
10
20
30
40
50
60
70
80
WT CD26
0
10
20
30
40
50
60
70
80
WT CD26
CFU-GM
HPCperFemur(x103)%inS-Phase
Control
GMCSF:Full Length (FL)
GMCSF:Truncated (T)
GMCSF:FL+T

16. Equilibrium receptor binding kinetic
analysis using the factor dependent human
cell line, TF-1, as well as primary purified
CD34+ cord blood cells demonstrated that:
• Truncated GM-CSF binds with higher affinity to GM-CSF receptor
than does full length GM-CSF
• Truncated GM-CSF can block binding of full length GM-CSF
• This supports the functional progenitor cell GM-CSF stimulation
assays that suggest that truncated GM-CSF can act as a negative
regulator of full length GM-CSF function.

17. pJAK2
15 minutes
5 minutes
15 minute ratios
30 minutes
Unstimulated
Full Length
Truncated
1:1
5/10
2.5/10
1.25/10
N = 3 expts
%Changeinmeanfluorescence
(mean+SE)
0
10
20
30
40
50
60
70
80
90
100
N = 3 expts
%Changeinmeanfluorescence
(mean+SE)
0
10
20
30
40
50
60
70
80
90
100
N = 3 expts
%Changeinmeanfluorescence
(mean+SE)
0
10
20
30
40
50
60
70
80
90
100
%Changeinmeanfluorescence
(mean+SE)
0
10
20
30
40
50
60
70
80
90
100
FL GM-CSF
T GM-CSF
1:1
2.5:10
1.25:10
p<0.001
p<0.001 p<0.001
N=1 exp
(TF1 Cells)

18. pSTAT5
Unstimulated
Full Length
Truncated
1:1
5/10
2.5/10
1.25/10
FL GM-CSF
T GM-CSF
1:1
2.5:10
1.25:10
N = 3 expts
%Changeinmeanfluorescence
(mean+SE)
0
10
20
30
40
50
60
70
80
90
100
15 minutes
5 minutes
30 minutes
30 minute ratios
%Changeinmeanfluorescence
(mean+SE)
0
10
20
30
40
50
60
70
80
90
100
N = 3 expts
%Changeinmeanfluorescence
(mean+SE)
0
10
20
30
40
50
60
70
80
90
100
N = 3 expts
%Changeinmeanfluorescence
(mean+SE)
0
10
20
30
40
50
60
70
80
90
100
p<0.002
p<0.004 p<0.004
N=1 exp
(TF1 Cells)

19. %Increaseinmeanflourescence
(mean±SE)
0
20
40
60
80
100
120
0
20
40
60
80
100
120
Truncated
Full Length
pJAK2
pSTAT5
GRAY = Untreated
BLUE = Truncated GM-CSF
RED = Full Length GM-CSF
N = 6 expts
N = 3 expts
Influence of Full Length and Truncated Human GM-CSF on Phosphorylation of
JAK2 and STAT5 in Human CD34+ Cord Blood Cells

20. Effects of CD26/DPPIV -/- In Vivo on
Recovery from Stress
(radiation and drugs)

21. a
NS
a
a
NS
NS
a
NS
NS
NS
NS
NS
0
1000
2000
3000
4000
5000
6000
7000
0 12 24 36 48
Cell Lysate: 400 rads
PLASMA: 400 rads
PLASMA: 650 rads
Cell Lysate: 650 rads
Hours post irradiation
RelativeLightUnits
DPPIV Activity in Plasma and Cell Lysates of Mice Pre- and Post- Radiation

22. CFU-GM
Progenitors/femur(thousands)
0
5
10
15
20
25
30
35
40
45
Days Post 400cGy Radiation
D0 D7 D10 D21
1.7X(<0.04)
3.6X(<0.006)
3.9X(<0.03)
9.4X(<0.001)
6.9X(<0.002)
1.9X
a
WT
WT+Sitagliptin
CD26-/-

23. 0
20
40
60
80
100
120
140
CFU-GM
Days Post 5FU
Progenitors/femur(thousands)
D0 D7 D10 D21
3.0X(<0.001)
1.8X(<0.004)
9.5X(<0.001)
7.1X(<0.002)
ND
WT
WT+Sitagliptin
CD26-/-

24. Control
Sitagliptin
(oral)
0
20
40
60
80
1 2 4 6
p=<0.001
p=<0.001
p=<0.001
p=<0.001
Primary Transplant
(Competitive)
Months (post transplant)
%Donor(CD45.2)Chimerism
9
p=<0.001
Effect of Oral Administration of DPP4 Inhibitor (Sitagliptin) to Lethally
Irradiated Recipient Mice on Engraftment of Mouse Bone Marrow Cells

25. In-vivo inhibition to enhance engraftment of
single-unit cord blood transplants in adults with
high-risk hematological malignancies
Farag, S.S., Srivastava, S., Messina-Graham, S., Schwartz, J.,
Nelson, R., Robertson, M., Abonour, R., Cornetta, K., Wood,
L., Secrest, A., Rojas, L., Strother, M.R., Jones, D., and
Broxmeyer, H.E.
Stem Cells & Development 22:1007-1015, 2013

26. Sherif Farag M.D.

27. Sitagliptin: A clinical DPP-4 inhibitor
• Specific DPP-4 inhibitor
• Only available PO
• FDA approved for treatment of type 2 diabetes
mellitus (DM)
• Extensively tested in healthy subjects
• Incretin stimulation of insulin release is glucose dependent;
hypoglycemia not observed even at high doses
• PK and PD well characterized in healthy volunteers
and patients with DM

28. Treatment Plan
Day of Transplantation
-7 -6 -5 -4 -3 -2 -1 0 +1 +2
TBI (165 cGy bid) X X X X
Cyclophosphamide
(60 mg/kg/day)
X X
ATG (12.5 mg/kg/day)* X X X
Sitagliptin (600 mg) X X X X
UCB transplantation X
Filgrastim 5 μg/kg/day SC starting day +5 until ANC ≥2.0x109/l
for 2 consecutive days
*ATG replaced by fludarabine 30 mg/m2 days -6 to -2 after
first 11 patients to reduce risk of infections

29. Comparison to NYBC Data on
engraftment of single UCB Units
Expected Outcome:
< 80% engraftment by day 77
50% engraft by day ~28-30
Rubenstein et al. NEJM 1998, 351:2276
CD26 Inhibition
Days after transplantation
Cumulativeincidence
ofneutrophilengraftment
Median days
to engraftment
21 days

30. Activity of Plasma DPPIV (RCD CB Unit Transplant)*
* Maximum inhibition occurred 2-4 hrs after dosing, with DPPIV activity ≥80% of
baseline by 16 hrs.
Pre-dose
0.5
1
2
4
8
12
16
24
2
4
8
16
24
2
4
8
16
24
2
4
8
16
24
0
10
20
30
40
50
60
70
80
90
100
110
120
130
140
150
Day -1 Day 0 Day +1 Day +2
Time after sitagliptin dose
PlasmaCD26Activity(%ofpre-doselevel)

31. Conclusions
• DPP4 enzyme activity in patients receiving
sitagliptin was suboptimal
• Opportunities to further improve the efficacy
of DPP-4 inhibition need to be explored:
• Pharmacodynamic studies in transplant patients suggest
that more frequent doses of sitagliptin are required for
sustained DPP-4 inhibition
• Longer duration of DPP-4 inhibition may be needed to take
harness positive effects on hematopoeitic cytokines
• Modification in conditioning regimen
• Multicenter phase II trial sponsored by NHLBI
is under development to confirm results

32. Influence of DPP4 Truncation on
Negative Regulators of
Hematopoiesis

33. Table 1. DPPIV Cleavage Sites on Human Chemokines
Chemokines N-terminus…
CCL2 / MCP-1 QPDAINAPVTCCYNFT
CCL3 / MIP1α APLAADTPTACCFSYT
CCL4 / MIP-1β APMGSDPPTACCFSY
CCL5 / RANTES SPYSSDTTPCCFAYIAR
CXCL4 / PF-4 EAEEDGDLQCLCVKT
CXCL5 / ENA-74 AAVLRELRCVCLQTTQ
CXCL5 / ENA-78 (non-cleavable) AGPAAAVLRELRCVCL
CXCL6 / GCP-2 GPVSAVLTELRCTCLR
CXCL8 / IL-8 SAKELRCQCIKTYSKP
CXCL8 / IL-8 (non-cleavable) AVLPRSAKELRCQCIK
CXCL9 / MIG TPVVRKGRCSCISTNQ
CXCL10 / IP-10 VPLSRTVRCTCISISNQ
XCL1 / Lymphotactin VGSEVSDKRTCVSLTT

34. (0.01)
(0.1)
(1)
(10)
CXCL4 (100)
(0.01)
(0.1)
(1)
(10)
CXCL10 (100)
(0.01)
(0.1)
(1)
(10)
CXCL9 (100)
(0.01)
(0.1)
(1)
(10)
CXCL6 (100)
(0.01)
(0.1)
(1)
(10)
CCL3 (100)
Control Medium
Percent Inhibition
Bl/6 +/+
0 20 40 60
Bl/6+/+ with
Diprotin A
0 20 40 60
Bl/6 CD26 -/-
0 20 40 60
Chemokine (ng/ml)

35. In Vitro
• Truncated chemokine is inactive as a
myelosuppressive molecule
• Truncated chemokine blocks
myelosuppression by that full length molecule

36. i) CCL3
Absolute Number Progenitors
per Femur (in thousands)
0
10
20
30
40
50
60
*
Control
Full Length (FL)
Truncated (TR)
FL+TR
0
10
20
30
0
5
ii) CXCL8
iii) CXCL9
0
10
20
30
40
50
CFU-GM
0
10
BFU-E CFU-GEMM
CFU-GM
*
**
*
*
*
0
20
40
60
80
100
*
0
20
40
60
80
100
Percent HPC
in S-Phase
0
20
40
60
80
100
CFU-GM
* * *
***
CFU-GM BFU-E CFU-GEMM
CFU-GM BFU-E CFU-GEMM CFU-GM BFU-E CFU-GEMM

37. DEK
• Mammalian nuclear phosphoprotein originally
identified as a fusion protein resulting from a t (6;9)
translocation of a rare subtype of AML
Von Linderm et al Mol Cell Biol 12:1687, 1992
• Bears little resemblance to other known proteins, but
is well conserved among higher eukaryotes
• In addition to its DNA-binding properties, it is found in
association with mRNA splicing and export factors, as
well as with spliced transcripts
• Plays an active role in maintaining higher order
chromatin architecture

38. DEK
• DEK can leave the cell, and in paracrine fashion, be
taken up by another cell, traffic to the nucleus of that
cell and in bioactive form modulate global chromatin
structure
David Markovitz and colleagues
University of Michigan, Ann Arbor, MI
PNAS in press

39. DEK Regulates Hematopoietic Stem
Engraftment and Progenitor Cell Proliferation
Broxmeyer, H.E., Kappes, F., Mor-Vakin, N., Legendre,
M., Kinzfogl, J., Cooper, S., Hangoc, G.,
and Markovitz, D.M.
Stem Cells and Development 21: 1449-1454, 2012

40. 0
10000
20000
30000
40000
Absolute Number of
Progenitors / Femur
p=0.003
p=0.108
p=0.044
CFU-GM BFU-E CFU-GEMM
WT DEK (-/-)
0
5000
10000
15000
20000
Absolute Number of
Progenitors /Spleen
p=0.006
p=0.001
p=0.129
CFU-GM BFU-E CFU-GEMM
0
20
40
60
80
100
Cycling: BM Progenitors
(% S-Phase)
p=0.001 p=0.003 p=0.001
CFU-GM BFU-E CFU-GEMM
0
20
40
60
80
100
Cycling: Spleen Progenitors
(% S-Phase)
p=0.001 p=0.001 p=0.001
CFU-GM BFU-E CFU-GEMM

41. DEK is myelosuppressive in vitro for
colony formation by mouse CFU-GM,
BFU-E, and CFU-GEMM

42. a) CFU-GM
b) BFU-E
c) CFU-GEMM
0 20 40 60 80 100
0.041
NS
NS
0.010
0.001
0.023
0.001
0.003
0.009
0.001
0.001
0.015
0.002
0.004
0.011
0.002
0.013
NS
0.001
0.001
0.001
0.003
NS
NS
0.001
0.001
0.001
Epo+SCF
Epo+GM-CSF+
IL3+SCF
IL3+SCF
GM-CSF
GM-CSF+SCF
0 25 50 75
Epo
Epo+SCF
Control
DEK (100nM)
DEK (1nM)
DEK (10nM)
Human Cord Blood Colony Numbers
Epo+GM-CSF+
IL3+SCF

43. 0 10 20 30 40 50
CFU-GEMM
BFU-E
CFU-GM
Control
DEK (100nM)
Percent wells with colony
p<0.0001
p= 0.020
p= 0.059

44. 0
20
40
60
80
100
1 2 4 6 1 3 5
Primary
Mouse Recipients
Peripheral Blood Bone Marrow Peripheral Blood
Secondary
Mouse Recipients
WT
DEK (-/-)
Months:
post transplant
NS NS p<0.002 p<0.04 p<0.002 p<0.002 p<0.002
%DonorCellChimerism
inCompetitiveRepopulatingAssay
a) b)

45. A Role For DEK in Stem/Progenitor Cell Biology
Broxmeyer, H.E., Mor-Vaknin, N., Kappes, F.,
Legendre, M., Saha, A.K., Ou, X., O’Leary, H.A.,
Capitano, M., Cooper, S., and Markovitz, D.M.
Stem Cells in press

46. 0 20 40 60 80
Control
FL DEK (50nM)
“ (10nM)
“ (1nM)
TR DEK (50nM)
“ (25nM)
FL DEK (50nM)+TR DEK (25nM)
“ + " (12.5nM)
“ + " (6.25nM)
0 25 50 75 100 125
Colony Formation
Exp #1 Exp #2
*, significantly different from control medium (p<0.05)
*
*
*
*
*
ND
ND
ND
Influence of full length (FL) and DPP4-treated (=truncated, TR) DEK
alone and in combination on 5x104 C57Bl/6 mouse BM cells/ml treated
with GM-CSF (Exp#1) or GM-CSF+SCF (Exp#2)

47. Potential Role for Dipeptidylpeptidase (DPP) 4
in Regulation of Many Different Cell and
Tissue Systems
Implications of DPP4 Modification of Proteins That Regulate
Stem/Progenitor and More Mature Cell Types
Ou, X., O’Leary, H.A., and Broxmeyer, H.E. 2013
Blood in press
The Role of DPP4 in Hematopoiesis and Transplantation
O’Leary, H.A., Ou, X., and Broxmeyer, H.E. 2013
Current Opinions in Hematopoiesis (Hematology) in press

48. Chemokines Cytokines
Peptide Species N-terminus Peptide Species N-terminus
CXCL1 /GRO-α M APIAN… a,b Epo H APPRL… a,b
CXCL2 /GRO-β/MIP-2α H APLAT… a,b Epo M APPRL… a,b
CXCL4 /PF4 H EAEED… a,b GM-CSF H APARS… a,b
CXCL5 /ENA-78 M APSSV… a,b GM-CSF M APTRS... a,b
CXCL6/GCP2 H GPVSA… a,b G-CSF H ATPLG… a,b
CXCL8/IL-8 H SAKEL… a,b G-CSF M VPLVT… a,b
CXCL9/MIG H TPVVR… a,b IL-3 H APMTQ... a,b
CXCL10/INP-10 H VPLSR… a,b IL-1 α H SAPFS… a,b
CXCL10/INP-10 M IPLAR… a,b IL-1 β H APVRS… a,b
CXCL11/I-TAC H IPLAR… a,b IL-1 α M SAPYT… a,b
CXCL12/SDF-1 H KPVSL… a,b IL-1 β M VPIRQ… a,b
CXCL12 (isoform α) M KPVSL… a,b IL-2 H APTSS… a,b
CXCL12 (isoform β) M KPVSL… a,b IL-2 M APTSS… a,b
CXCL12( isoform γ) M QPDAI… a,b IL-5 H IPTEI… a,b
CCL2/MCP-1 H QPDAV… a,b IL-6 H VPPGE… a,b
CCL2/MCP-1 M APYGA… a,b IL-6 M FPTSQ… a,b
CCL3 /MIP-1α/LD78α M APLAA… a,b IL-8 (6-77) H SAEKL… a,b
CCL3-L1/LD78β H APMGS… a,b IL-10 H SPGQG… a,b
CCL4 /MIP-1β H APMGS… a,b IL-13 H GPVPP… a,b
CCL4 /MIP-1β M APMGS… a,b IL-17B H QPRSP… a,b
CCL5/RANTES H SPYSS… a,b IL-17A M AAIIP… a,b
CCL5/RANTES M SPYGS… a,b IL-17C M DPPSW…a,b
CCL7/MCP-3 H QPVGI… a,b IL-22 H APISS… a,b
CCL7/MCP-3 M QPDGP… a,b IL-22 M LPVNT… a,b
CCL8/MCP-2 H QPDSV… a,b IL-23 α H RAVPG… a,b
CCL11/Eotaxin H GPASV… a,b IL-23 α M VPRSS… a,b
CCL11/Eotaxin M HPGSI... a,b IL-27 α H FPRPP… a,b
CCL12/MCP-5 M GPDAV... a,b IL-27 α M FPTDP… a,b
CCL16/HCC-4/LEC/LCC-1/LMC H QPKVP… a,b IL-28A H VPVAR… a,b
CCL19/CKβ11/MIP-3β/ELC/Exodus-3 M GANDA… a,b IL-28B H VPVAR… a,b
CCL22/MDC/STCP-1 H GPYGA… a,b IL-28A M DPVPR… a,b
CCL22/MDC/STCP-1 M GPYGA… a,b IL-28B M DPVPR… a,b
CCL26/Eotaxin-3/MIP-4α M HPGSI… a,b IL-29 H GPVPT… a,b
CCL27/CTACK/ILC/ESKINE M LPLPS… a,b
Chemokines/Cytokines with putative penultimate (Alanine/Proline) truncation site for DPP4

49. Modulatory Factors with putative penultimate (Alanine/Proline) truncation site for DPP4
(part 1)
Modulatory Factors
Peptide Species N-terminus Peptide Species N-terminus
Adipsin (propeptide) H PPRGR… a,b GDF-1 H DAEPV… a,b
Adipsin (propeptide) M QPRGR…a,b GDF-3 H AAIPV…a,b
α-1 microglobulin H GPVPT… a,b GDF-3 M AAISV… a,b
α-1 microglobulin M DPAST… a,b GDF-5 H APLAT… a,b
ANGPTL4 (isoform a) H GPVQS…a,b GDF-5 M APLAN… a,b
ANGPTL4 (isoform b) H GPVQS…a,b GDF 6 H TAFAS… a,b
ANGPTL6 H RAGAP…a,b GDF 6 M TAFAS… a,b
BDNF (propeptide) H APMKE…a,b GDF-7 H TALAG… a,b
BDNF (propeptide) M APMKE...a,b GDF-7 M TALAG… a,b
bFGF H PALPE… a,b GDF-8 H GPVDL… a
bFGF M PALPE… a,b GDNF (propeptide) H SPDKQ…a,b
Bradykinin H RPPGF…a,b GDNF (propeptide) M SPDKQ… a,b
Bradykinin M RPPGF… a,b GHRH H YADAI… a,b
BMP-4 H SPKHH…a,b GLP-1 (7-36) H HAEGT… a,b
BMP-4 M SPKHH…a,b GLP-2 H HADGS… a,b
BMP-5 H AANKR… a,b GRP H VPLPA…a,b
BMP-5 M AASKR… a,b GRP M APVST… a,b
c1qTNF5 H SPPLD… a,b HCG α H APDVQ… a,b
c1qTNF5 M SPPLD…a,b HCG α M LPDGD… a,b
Chromogranin H LPVNS… a,b IGF-1 isoform 1 H GPETL… a,b
Chromogranin M LPVNS…a,b IGF-1 isoform 2 H GPETL… a,b
DKK 3 H APAPT…a,b IGF-1 isoform 3 H GPETL… a,b
DNER H NPVPA… a,b IGF-1 isoform 4 H GPETL… a,b
Enterostatin H APGPR... a,b IGF-1 isoform 1 M GPETL… a,b
Enterostatin M APGPR…a,b IGF-1 isoform 2 M GPETL… a,b
IGF-1 isoform 3 M GPETL…a,b
IGF-1 isoform 4 M GPETL… a,b
IGF-1 isoform 5 M GPETL… a,b

50. Modulatory Factors with putative penultimate (Alanine/Proline) truncation site for DPP4
(part 2)
Modulatory Factors
Peptide Species N-terminus Peptide Species N-terminus
Inhibin alpha chain (propeptide) H HALGG…a,b RBP3 H GPTHL… a,b
Inhibin alpha chain (propeptide) M HAVGG… a,b RBP3 M GPTHL…a,b
Inhibin beta E chain H TPTCE… a,b Somatotropin isoform 1 H FPTIP… a,b
Inhibin beta E chain M TPTCE… a,b Somatotropin isoform 2 H FPTIP… a,b
Lactoferrin M KATTV… a,b Somatotropin isoform 3 H FPTIP… a,b
leptin H VPIQK… a,b Somatotropin isoform 4 H FPTIP… a,b
leptin M VPIQK… a,b Somatotropin M FPAMP… a,b
LIF H SPLPI… a,b Transferrin H VPDKT… a,b
LIF M SPLPI… a,b Transferrin M VPDKT… a,b
LTα H LPGVG… a,b Trypsinogen H APFDD… a,b
Neurotrophin-3 H YAEHK... a,b Vasostatin-1 H LPVNS… a,b
Neurotrophin-3 M YAEHK… a,b Vasostatin-2 H LPVNS… a,b
Notch 3 H APPCL… a,b VEGF A isoform i H APMAE… a,b
Notch 3 M APPCL… a,b VEGF A isoform k H APMAE…a,b
NPY H YPSKP… a,b VEGF A isoform l H APMAE… a,b
NPY M YPSKP… a,b VEGF A isoform m H APMAE… a,b
Oncostatin M H AAIGS… a,b VEGF A isoform n H APMAE… a,b
Osteopontin H IPVKQ… a,b VEGF A isoform o H APMAE… a,b
Osteopontin M LPVKV… a,b VEGF A isoform p H APMAE… a,b
PDGFD M TPQRA…a,b VEGF A isoform 1 M APTTE…a,b
Peptide YY H YPIKP… a,b VEGF A isoform 2 M APTTE… a,b
Peptide YY M YPAKP… a,b VEGF A isoform 3 M APTTE… a,b
Prolactin H LPICP…a,b Wnt 9b M AAYFG… a,b
Prolactin M LPICS…a,b Wnt 10a H MPRSA... a,b
Wnt 10a M VPRSA… a,b

51. Peptides Species N-terminus Peptides Species N-terminus
CXCL1 H ASVAT… a,b ANGPT2 M YSNFR… a,b
CXCL3 H ASVVT… a,b BDNF H HSDPA… a,b
CXCL7 H SSTKG… a,b BDNF M HSDPA… a,b
CXCL7 M KSDGM… a,b DLL3 M HSFGP… a,b
CCL1 H KSMQV… a,b DLL4 M GSGIF…a,b
CCL1 M KSMLT… a,b DKK 3 M PSPTV… a,b
CCL20 H ASNFD… a,b FZD6 H HSLFT… a,b
CCL20 M ASNYD… a,b FZD6 M HSLFT… a,b
IL-3 M ASISG… a,b Glucagon M HSQGT…a,b
IL-17E M VSLRI… a,b Glucagon M HSQGT…a,b
IFN-β H MSYN… a,b GM2A H SSFSW…a,b
LTα M LSGVR… a,b Beta NGF H SSSHP… a,b
TGF-β1 H LSTCK… a,b Beta NGF M SSTHP… a,b
TGF-β1 M LSTCK… a,b PACAP (1-27) H HSDGI… a,b
TNF-β M LSGVR… a,b PACAP (1-38) H HSDGI… a,b
TNF (Membrane Form) H MSTES… a,b PDGFC M ESNLS… a,b
TNF (Membrane Form) M MSTES… a,b PDGFC H ESNLS… a,b
DEK H MSASA… a,b Wnt 8a M ASAWS… a,b
DEK M MSAAA… a,b Wnt 8b H WSVNN… a,b
Factors with putative truncation site (Serine) for DPP4

52. Potential Models for DPP4 Activity

55. Lab Members
Former Lab Members
Scott Cooper, M.S.
Research Associate
Giao Hangoc, D.V.M.
Research Associate
Charlie Mantel, B.S.
Research Associate
Hal E Broxmeyer, Ph.D.
Man Ryul Lee, PhD
Post Doc
Xuan Ou, Ph.D
Post Doc
Heather O’Leary, Ph.D
Post Doc
Sunanda Basu , Ph.D..Sara RohrabaughYoung-June Kim, Ph.D. Ying Liu , Ph.D.
Tammi Taylor, Ph.D.Timothy Campbell, M.D., Ph.D.Kent W. Christophersen II, PhD John Kinzfogl, Ph,D.Myung Kwan Han, PhD
Hee-Don Chae, Ph.D.
Steven Messina-Graham
Grad Student
Xinxin Huang, PhD
Post Doc
Maegan Capitano, Ph.D
Post Doc